Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response.
G72 (syn. DAOA, D-amino acid oxidase activator) is a susceptibility gene for both schizophrenia and bipolar disorder. Diffusion tensor imaging studies hint at changes in fiber tract integrity in both disorders. We aimed to investigate whether a G72 susceptibility haplotype causes changes in fiber tract integrity in young healthy subjects. We compared fractional anisotropy in 47 subjects that were either homozygous for the M23/M24 risk haplotype (n = 20) or homozygous for M23(rs3918342)/M24(rs1421292) wild type (n = 27) using diffusion tensor imaging with 3 T. Tract-based spatial statistics, a method especially developed for diffusion data analysis, was used to delineate the major fiber tracts. We found clusters of increased FA values in homozygous risk haplotype carriers in the right periinsular region and in the right inferior parietal lobe (IPL). We did not find clusters indicating decreased FA values. The insula and the IPL have been implicated in both schizophrenia and bipolar pathophysiology. Increased FA values might reflect changes in dendritic morphology as previously described by in vitro studies. These findings further corroborate the hypothesis that a shared gene pool between schizophrenia and bipolar disorder might lead to neuroanatomic changes that confer an unspecific vulnerability for both disorders.
Patients with borderline personality disorder (BPD) suffer from various impairments in emotional functioning such as affective instability, inappropriate anger and unstable relationships. These deficits may influence two fundamental motivational systems, the behavioral inhibition system (BIS) and behavioral activation system (BAS). To investigate behavioral intentions and possible impairments in BPD we applied an implicit joystick task to measure implicit behavioral tendencies in response to facial expressions (happiness, sadness, anger, fear and neutral) in 25 patients with BPD and matched 25 healthy controls (HC). Additionally, we evaluated explicit approach and avoidance reactions to these social stimuli, emotion recognition abilities and subjective behavioral ratings. Our data analysis suggests that, although BPD patients accurately identified facial emotional expressions and reacted to them similarly as HC in the joystick task, they had significantly stronger avoidance tendencies in the rating task, especially for happiness and fear. On top of this they exhibited increased BIS sensitivity and decreased BAS sensitivity in the self-report measures. Possible influences are maladaptive cognitive schemas, high negative affect, insecure attachment style and a negative evaluation bias. The observed dysfunctional avoidance ratings may influence the appraisal of socially relevant stimuli and therefore adds further knowledge on social interaction problems in BPD.
Depression often involves anxiety symptoms and shows a strong comorbidity with panic disorder. However, the neural basis is unclear. The aim of the current study was to use semantic priming to investigate the neural correlates of panic and anxiety-related information processing in depression. In a lexical decision task, panic/agoraphobia-disorder-related and neutral word-pairs were presented during functional magnetic resonance imaging. Participants comprised 19 patients with major depression but without comorbid anxiety and 19 demographically matched controls. On a behavioral level, comparable significant priming effects were found for the neutral condition, while only patients showed a significant inhibition effect (slower reaction time for panic-related stimuli) for the panic condition. On a neural level, significant group differences emerged in left fronto-parietal (enhanced activation for patients) and left temporo-occipital regions (reduced activation for patients). The results showed that depressed patients recruit not only areas related to the interaction of emotion and semantic processing but also regions that are related to fear circuitry to process panic-related information. Hence, in the context of depression, there seems to be a pathological processing of panic-related information that could play an important role during the disorder and should be considered.
Up to now, it remains unclear how monoamine oxidase A (MAOA), which has been repeatedly linked to aggression, affects brain activity within resting-state networks (RSN). Here, we used functional magnetic resonance imaging (fMRI) to test whether the MAOA genotype might influence activity within the common RSN. Our results demonstrate that during rest, participants with the low-activity genotype (MAOA-L) exhibit more activity within frontoparietal and temporal parts of the default mode network (DMN) and the cerebellum. The executive control and salience RSN revealed reduced activity for the MAOA-L group in several areas related to executive control, namely the right middle frontal gyrus (BA 6 and BA 9), and the dorsal part of the anterior cingulate cortex. Participants with the high-activity genotype (MAOA-H) showed increased activity in the posterior cingulate part of the DMN. Taken together, we found widespread hyperactivity within the DMN and reduced activity in brain areas related to executive and inhibitory control for the MAOA-L group. We discuss how these first results examining the influence of MAOA on the resting brain might be related to previous findings regarding the genetics of aggression, while acknowledging that this is an exploratory study which needs further confirmation.
Several studies suggest facial affect perception (FAP) deficits in schizophrenia are linked to poorer social functioning. However, whether reduced functioning is associated with inaccurate perception of specific emotional valence or a global FAP impairment remains unclear. The present study examined whether impairment in the perception of specific emotional valences (positive, negative) and neutrality were uniquely associated with social functioning, using a multimodal social functioning battery. A sample of 59 individuals with schizophrenia and 41 controls completed a computerized FAP task, and measures of functional capacity, social competence, and social attainment. Participants also underwent neuropsychological testing and symptom assessment. Regression analyses revealed that only accurately perceiving negative emotions explained significant variance (7.9%) in functional capacity after accounting for neurocognitive function and symptoms. Partial correlations indicated that accurately perceiving anger, in particular, was positively correlated with functional capacity. FAP for positive, negative, or neutral emotions were not related to social competence or social attainment. Our findings were consistent with prior literature suggesting negative emotions are related to functional capacity in schizophrenia. Furthermore, the observed relationship between perceiving anger and performance of everyday living skills is novel and warrants further exploration.
Changes in fiber tract architecture have gained attention as a potentially important aspect of schizophrenia neuropathology. Although the exact pathogenesis of these abnormalities yet remains to be elucidated, a genetic component is highly likely. Neuregulin-1 (NRG1) is one of the best-validated schizophrenia susceptibility genes. We here report the impact of the Neuregulin-1 rs35753505 variant on white matter structure in healthy young individuals with no family history of psychosis.
Cognitive neuroscience research on semantics recognizes a distinction between categorical and associated relations. However, associations can be divided further, such as into part-whole and functional relations. We investigated the neural basis of both relations using a picture-word interference task in an fMRI study. While the left supramarginal gyrus and the right inferior temporal sulcus were activated by part-whole over functional relations, the same applies to the right parahippocampal complex contrasting the functional over part-whole relations. The small effect sizes of our analyses have to be interpreted with caution. While the parahippocampal complex might reflect global scene processing across objects, the inferior temporal sulcus might be involved in the perceptual encoding of object related knowledge and the supramarginal gyrus might represent a convergence zone which implements within object related perceptual features. The current study gives a first indication that the neural bases for part-whole and functional relations seem to be distinguishable.
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.
A primary function of cognitive control is to adjust the cognitive system according to situational demands. The so-called "conflict adaptation effect" elicited in laboratory experiments is supposed to reflect the above function. Neuroimaging studies suggest that adaptation of nonemotional conflict is mediated by the dorsolateral prefrontal cortex through a top-down enhancement of task-relevant (target), relative to task-irrelevant (distractor), stimulus representation in the sensory cortices. The adaptation of emotional conflict, on the other hand, is suggested to be related to the rostral anterior cingulate inhibiting the processing of emotional distractors through a top-down modulation of amygdala responsivity. In the present study, we manipulated, on a trial-by-trial basis, the levels of semantic interference conflict triggered by the incompatibility between emotional faces (targets) and emotional words (distractors) in a modified version of the emotional Stroop task. Similar to previous observations involving nonemotional interference effects, the behavioral adaptation of emotional conflict was found to be paralleled by a stronger recruitment of the fusiform face area. Additional areas related to the conflict adaptation effect were the bilateral insula, the bilateral frontal operculum (fO), the right amygdala, the left precentral and postcentral gyri, and the parietal cortex. These findings suggest that augmentation of cortical responses to task-relevant information in emotional conflict may be related to conflict adaptation processes in a way that has been observed in nonemotional conflict, challenging the view that brain circuitries underlying the conflict adaptation effect depend only on the nature of conflict. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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.
The ability to process multi-digit numbers is an essential skill which we investigated using a number decision task. Subjects were asked to decide whether a target number (e.g., 649) is too small or too large to be the mean between two delimiter numbers that constituted the interval (e.g., 567 and 715). Three-digit numbers were presented vertically with (1) growing interval sizes (i.e., distance between the two delimiters; e.g., interval size between 567 and 715 is 148) and target gap to the mean (e.g., the gap between the real mean 641 and the target 649 is 8) and (2) growing interval sizes with constant gap to the mean (i.e., for each interval size the gap between target and mean was held constant). The results showed that target gap to the mean "masked" the influence of interval sizes, i.e., subjects performance improved with increasing interval sizes (distance effect). This effect was reversed when constant target gaps to the mean and growing interval sizes were presented. These results were replicated presenting the numbers horizontally and with two-digit numbers. Additionally, a significant influence of decade but no effect of unit compatibility on reaction times and error rates, on number magnitude (size effect) and response format was found. Overall, we showed that the number decision task is an efficient tool to investigate multidigit number representation and the results from the experiments revealed evidence for a hybrid model of multi-digit number representation in which numbers are represented as a whole but also on separate mental number lines that interact with each other.
The aim of the present study was to investigate the impact of part-whole (e.g., car-motor) and functional associations (e.g., car-garage) on single word (Experiment 1) and sentence production (Experiment 2). In Experiment 1, a classical picture-word task was used. In Experiment 2, the same stimuli and distractors were embedded into a sentence. The relation between target and distractor was either part-whole, functional or unrelated. At single word level, part-whole and functional relations facilitate naming. Additionally, the facilitation effect was stronger for part-whole in comparison to functional associations. During sentence production, facilitation shifted to interference. The difference between both relations disappeared. The findings of the different effects between functional and part-whole associations depend on the length of utterances and highlight the divergent impact of associations. The differences between part-whole and functional associations in single word production might reflect a differential organization of associative links at the conceptual level. In contrast, during sentence production the syntactic processing at the lexical level seem to be more important than types of semantic associations at the conceptual level.
Schizophrenia patients have deficits in cognitive control as well as in a number of emotional domains. The antisaccade task is a measure of cognitive control that requires the inhibition of a reflex-like eye movement to a peripheral stimulus. Antisaccade performance has been shown to be modulated by the emotional content of the peripheral stimuli, with emotional stimuli leading to higher error rates than neutral stimuli, reflecting an implicit emotion processing effect. The aim of the present study was to investigate the impact on antisaccade performance of threat-related emotional facial stimuli in schizophrenia patients, first-degree relatives of schizophrenia patients and healthy controls. Fifteen patients, 22 relatives and 26 controls, matched for gender, age and verbal intelligence, carried out an antisaccade task with pictures of faces displaying disgusted, fearful and neutral expressions as peripheral stimuli. We observed higher antisaccade error rates in schizophrenia patients compared to first-degree relatives and controls. Relatives and controls did not differ significantly from each other. Antisaccade error rate was influenced by the emotional nature of the stimuli: participants had higher antisaccade error rates in response to fearful faces compared to neutral and disgusted faces. As this emotional influence on cognitive control did not differ between groups we conclude that implicit processing of emotional faces is intact in patients with schizophrenia and those at risk for the illness.
Deficits in response inhibition and heightened impulsivity have been linked to psychiatric disorders and aggression. They have been investigated in clinical groups as well as individuals with trait characteristics, yielding insights into the underlying neural and behavioral mechanisms of response inhibition and impulsivity. The motor inhibition tasks employed in most studies, however, have lacked an emotional component, which is crucial given that both response inhibition and impulsivity attain salience within a socio-emotional context. For this fMRI study, we selected a group with high trait aggression (HA, n=17) and one with low trait aggression (LA, n=16) from 550 males who had completed an Aggression Questionnaire. Neural activation was compared to an emotional version (including angry and neutral faces) of the stop signal task. Behavioral results revealed impaired response inhibition in HA, associated with higher motor impulsivity. This was accompanied by attenuated activation in brain regions involved in response inhibition, including the pre-supplementary motor area (SMA) and motor cortex. Together, these findings offer evidence that a reduced inhibition capacity is present in HA. Notably, response inhibition improved during anger trials in both groups, suggesting a facilitation effect through heightened activation in the related brain regions. In both groups, inclusion of the anger stimuli enhanced the activation of the motor and somatosensory areas, which modulate executive control, and of limbic regions including the amygdala. In summary, the investigation of response inhibition in individuals with high and low trait characteristics affords useful insights into the underlying distinct processing mechanisms. It can contribute to the investigation of trait markers in a clinical context without having to deal with the complex mechanisms of a clinical disorder itself. In contrast, the mechanisms of emotional response inhibition did not differ between groups. Hence, the specific emotional influence is not interacting with trait aggression.
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.
Emotional reactivity and the ability to modulate an emotional state, which are important factors for psychological well-being, are often dysregulated in psychiatric disorders. Neural correlates of emotional states have mostly been studied at the group level, thereby neglecting individual differences in the intensity of emotional experience. This study investigates the relationship between brain activity and interindividual variation in subjective affect ratings. A standardized mood induction (MI) procedure, using positive facial expression and autobiographical memories, was applied to 54 healthy participants (28 female), who rated their subjective affective state before and after the MI. We performed a regression analysis with brain activation during MI and changes in subjective affect ratings. An increase in positive affective ratings correlated with activity in the amygdala, hippocampus and the fusiform gyrus (FFG), whereas reduced positive affect correlated with activity of the subgenual anterior cingulate cortex. Activations in the amygdala, hippocampus and FFG are possibly linked to strategies adopted by the participants to achieve mood changes. Subgenual cingulate cortex activation has been previously shown to relate to rumination. This finding is in line with previous observations of the subgenual cingulates role in emotion regulation and its clinical relevance to therapy and prognosis of mood disorders.
Patients with schizophrenia have semantic processing disturbances leading to expressive language deficits (formal thought disorder). The underlying pathology has been related to alterations in the semantic network and its neural correlates. Moreover, crossmodal processing, an important aspect of communication, is impaired in schizophrenia. Here we investigated specific processing abnormalities in patients with schizophrenia with regard to modality and semantic distance in a semantic priming paradigm. Fourteen patients with schizophrenia and fourteen demographically matched controls made visual lexical decisions on successively presented word-pairs (SOA = 350 ms) with direct or indirect relations, unrelated word-pairs, and pseudoword-target stimuli during fMRI measurement. Stimuli were presented in a unimodal (visual) or crossmodal (auditory-visual) fashion. On the neural level, the effect of semantic relation indicated differences (patients > controls) within the right angular gyrus and precuneus. The effect of modality revealed differences (controls > patients) within the left superior frontal, middle temporal, inferior occipital, right angular gyri, and anterior cingulate cortex. Semantic distance (direct vs. indirect) induced distinct activations within the left middle temporal, fusiform gyrus, right precuneus, and thalamus with patients showing fewer differences between direct and indirect word-pairs. The results highlight aberrant priming-related brain responses in patients with schizophrenia. Enhanced activation for patients possibly reflects deficits in semantic processes that might be caused by a delayed and enhanced spread of activation within the semantic network. Modality-specific decreases of activation in patients might be related to impaired perceptual integration. Those deficits could induce and increase the prominent symptoms of schizophrenia like impaired speech processing.
Emotional and non-emotional Stroop are frequently applied to study major depressive disorder (MDD). The versions of emotional Stroop used in previous studies were not, unlike the ones employed in the present study, based on semantic incongruence, making it difficult to compare the tasks.
The rapid demographical shift occurring in our society implies that understanding of healthy aging and age-related diseases is one of our major future challenges. Sensory impairments have an enormous impact on our lives and are closely linked to cognitive functioning. Due to the inherent complexity of sensory perceptions, we are commonly presented with a complex multisensory stimulation and the brain integrates the information from the individual sensory channels into a unique and holistic percept. The cerebral processes involved are essential for our perception of sensory stimuli and becomes especially important during the perception of emotional content. Despite ongoing deterioration of the individual sensory systems during aging, there is evidence for an increase in, or maintenance of, multisensory integration processing in aging individuals. Within this comprehensive literature review on multisensory integration we aim to highlight basic mechanisms and potential compensatory strategies the human brain utilizes to help maintain multisensory integration capabilities during healthy aging to facilitate a broader understanding of age-related pathological conditions. Further our goal was to identify where further research is needed.
A successful reciprocal evaluation of social signals serves as a prerequisite for social coherence and empathy. In a previous fMRI study we studied naturalistic communication situations by presenting video clips to our participants and recording their behavioral responses regarding empathy and its components. In two conditions, all three channels transported congruent emotional or neutral information, respectively. Three conditions selectively presented two emotional channels and one neutral channel and were thus bimodally emotional. We reported channel-specific emotional contributions in modality-related areas, elicited by dynamic video clips with varying combinations of emotionality in facial expressions, prosody, and speech content. However, to better understand the underlying mechanisms accompanying a naturalistically displayed human social interaction in some key regions that presumably serve as specific processing hubs for facial expressions, prosody, and speech content, we pursued a reanalysis of the data. Here, we focused on two different descriptions of temporal characteristics within these three modality-related regions [right fusiform gyrus (FFG), left auditory cortex (AC), left angular gyrus (AG) and left dorsomedial prefrontal cortex (dmPFC)]. By means of a finite impulse response (FIR) analysis within each of the three regions we examined the post-stimulus time-courses as a description of the temporal characteristics of the BOLD response during the video clips. Second, effective connectivity between these areas and the left dmPFC was analyzed using dynamic causal modeling (DCM) in order to describe condition-related modulatory influences on the coupling between these regions. The FIR analysis showed initially diminished activation in bimodally emotional conditions but stronger activation than that observed in neutral videos toward the end of the stimuli, possibly by bottom-up processes in order to compensate for a lack of emotional information. The DCM analysis instead showed a pronounced top-down control. Remarkably, all connections from the dmPFC to the three other regions were modulated by the experimental conditions. This observation is in line with the presumed role of the dmPFC in the allocation of attention. In contrary, all incoming connections to the AG were modulated, indicating its key role in integrating multimodal information and supporting comprehension. Notably, the input from the FFG to the AG was enhanced when facial expressions conveyed emotional information. These findings serve as preliminary results in understanding network dynamics in human emotional communication and empathy.
Antisocial behavior and aggression are prominent symptoms in several psychiatric disorders including antisocial personality disorder. An established precursor to aggression is a frustrating event, which can elicit anger or exasperation, thereby prompting aggressive responses. While some studies have investigated the neural correlates of frustration and aggression, examination of their relation to trait aggression in healthy populations are rare. Based on a screening of 550 males, we formed two extreme groups, one including individuals reporting high (n=21) and one reporting low (n=18) trait aggression. Using functional magnetic resonance imaging (fMRI) at 3T, all participants were put through a frustration task comprising unsolvable anagrams of German nouns. Despite similar behavioral performance, males with high trait aggression reported higher ratings of negative affect and anger after the frustration task. Moreover, they showed relatively decreased activation in the frontal brain regions and the dorsal anterior cingulate cortex (dACC) as well as relatively less amygdala activation in response to frustration. Our findings indicate distinct frontal and limbic processing mechanisms following frustration modulated by trait aggression. In response to a frustrating event, HA individuals show some of the personality characteristics and neural processing patterns observed in abnormally aggressive populations. Highlighting the impact of aggressive traits on the behavioral and neural responses to frustration in non-psychiatric extreme groups can facilitate further characterization of neural dysfunctions underlying psychiatric disorders that involve abnormal frustration processing and aggression.
Attentional deficits are prominent in schizophrenia, affecting nearly all cognitive functions. Human attention comprises three essential components: alerting, orienting and executive control. For the assessment of these functions, the attention network test (ANT) has been proposed and used in healthy controls and patients. In schizophrenia, the ANT has revealed behavioral deficits; however, the corresponding neural correlates have not been examined. In the present study, neural correlates of attention were investigated in 17 schizophrenia patients and 17 healthy controls using the ANT with fMRI. Behavioral deficits emerged in the alertness system with a reduced efficiency for temporal cues. In fMRI, changes were observed for all three domains-alerting, orienting and conflict-and revealed hyper- as well as hypoactivation in patients. Affected regions during alerting comprised a broad fronto-temporo-parieto-occipito-cerebellar network, while differences during orienting mainly tapped fronto-parietal regions and during conflict processing a thalamo-frontal-temporal occipital network including the postcentral regions. In general, hyperactivations were positively correlated with more severe psychopathologial symptoms.
Endophenotypes are intermediate phenotypes which are considered a more promising marker of genetic risk than illness itself. While previous research mostly used cognitive deficits, emotional functions are of greater relevance for bipolar disorder regarding the characteristic emotional hyper-reactability and deficient social-emotional competence. Hence, the aim of the present study was to clarify whether empathic abilities can serve as a possible endophenotype of bipolar disorder by applying a newly developed task in bipolar patients and their first-degree relatives. Three components of empathy (emotion recognition, perspective taking and affective responsiveness) have been assessed in a sample of 21 bipolar patients, 21 first-degree relatives and 21 healthy controls. Data analysis indicated significant differences between controls and patients for emotion recognition and affective responsiveness but not for perspective taking. This shows that in addition to difficulties in recognizing facial emotional expressions, bipolar patients have difficulties in identifying emotions they would experience in a given situation. However, the ability to take the perspective of another person in an emotional situation was intact but decreased with increasing severity of residual hypomanic and depressive symptoms. Relatives performed comparably bad on emotion recognition but did not differ from controls or patients in affective responsiveness. This study is the first to show that deficient emotion recognition is the only component of empathy which forms a possible endophenotype of bipolar disorder. This has important implications for prevention strategies. Furthermore, changes in affective responsiveness in first-degree relatives show a potential resilience marker.
Successful human interaction is based on correct recognition, interpretation, and appropriate reaction to facial affect. In depression, social skill deficits are among the most restraining symptoms leading to social withdrawal, thereby aggravating social isolation and depressive affect. Dysfunctional approach and withdrawal tendencies to emotional stimuli have been documented, but the investigation of their neural underpinnings has received limited attention. We performed an fMRI study including 15 depressive patients and 15 matched, healthy controls. All subjects performed two tasks, an implicit joystick task as well as an explicit rating task, both using happy, neutral, and angry facial expressions. Behavioral data analysis indicated a significant group effect, with depressed patients showing more withdrawal than controls. Analysis of the functional data revealed significant group effects for both tasks. Among other regions, we observed significant group differences in amygdala activation, with patients showing less response particularly during approach to happy faces. Additionally, significant correlations of amygdala activation with psychopathology emerged, suggesting that more pronounced symptoms are accompanied by stronger decreases of amygdala activation. Hence, our results demonstrate that depressed patients show dysfunctional social approach and withdrawal behavior, which in turn may aggravate the disorder by negative social interactions contributing to isolation and reinforcing cognitive biases.
Research on social cognition focuses on several human abilities with a huge diversity in the approaches to tap the different functions. Empathy, for instance, is a rather elaborated human ability, and several recent studies point to significant impairments in patients suffering from psychiatric disorders, such as schizophrenia or autism. Neuroimaging data from these patients commonly indicate neural dysfunctions accompanying the behavioral deficits. Studying the neural correlates of social cognition is of particular importance, because deficits in these domains may explain the major dysfunctions in psychiatric disorders that prevent effective (re) integration into work and social life. It has also become clearer that social cognition deficits, similar to emotion dysfunctions, may represent trait markers and endophenotypes of the diseases. However, there are several challenges for future studies on social cognitive dysfunctions: on the one hand, the complexity of the constructs and thus the variety of definitions which make it hard to develop adequate tasks. On the other hand, results are needed that particularly address the disorder specificity of these impairments, as well as their potential as endophenotypes via analyzing people at high-risk and their relatives.
Schizophrenia is a severe neuropsychiatric disorder with high heritability, though its exact etiopathogenesis is yet unknown. An increasing number of studies point to the importance of white matter anomalies in the pathophysiology of schizophrenia. While several studies have identified the impact of schizophrenia susceptibility gene variants on gray matter anatomy in both schizophrenia patients and healthy risk variant carriers, studies dealing with the impact of these gene variants on white matter integrity are still scarce. We here present a study on the effects of a Dysbindin schizophrenia susceptibility gene variant on fiber tract integrity in healthy young subjects. 101 subjects genotyped for Dysbindin-gene variant rs1018381, though without personal or first degree relative history of psychiatric disorders underwent diffusion tensor imaging (DTI), 83 of them were included in the final analysis. We used Tract-Based Spatial Statistics (TBSS) analysis to delineate the major fiber tracts. Carriers of the minor allele T of the rs1018381 in the Dysbindin gene showed two clusters of reduced fractional anisotropy (FA) values in the perihippocampal region of the right temporal lobe compared to homozygote carriers of the major allele C. Clusters of increased FA values in T-allele carriers were found in the left prefrontal white matter, the right fornix, the right midbrain area, the left callosal body, the left cerebellum and in proximity of the right superior medial gyrus. Dysbindin has been implicated in neurite outgrowth and morphology. Impairments in anatomic connectivity as found associated with the minor Dysbindin allele in our study may result in increased risk for schizophrenia due to altered fiber tracts.
The connection between cholinergic transmission and cognitive performance has been established in behavioural studies. The specific contribution of the muscarinic receptor system on cognitive performance and brain activation, however, has not been evaluated satisfyingly. To investigate the specific contribution of the muscarinic transmission on neural correlates of working memory, we examined the effects of scopolamine, an antagonist of the muscarinic receptors, using functional magnetic resonance imaging (fMRI). Fifteen healthy male, non-smoking subjects performed a fMRI scanning session following the application of scopolamine (0.4 mg, i.v.) or saline in a placebo-controlled, repeated measure, pseudo-randomized, single-blind design. Working memory was probed using an n-back task. Compared to placebo, challenging the cholinergic transmission with scopolamine resulted in hypoactivations in parietal, occipital and cerebellar areas and hyperactivations in frontal and prefrontal areas. These alterations are interpreted as compensatory strategies used to account for downregulation due to muscarinic acetylcholine blockade in parietal and cerebral storage systems by increased activation in frontal and prefrontal areas related to working memory rehearsal. Our results further underline the importance of cholinergic transmission to working memory performance and determine the specific contribution of muscarinic transmission on cerebral activation associated with executive functioning.
Navigation based on chemosensory information is one of the most important skills in the animal kingdom. Studies on odor localization suggest that humans have lost this ability. However, the experimental approaches used so far were limited to explicit judgements, which might ignore a residual ability for directional smelling on an implicit level without conscious appraisal.
Emotions influence our everyday life in several ways. With the present study, we wanted to examine the impact of emotional information on neural correlates of semantic priming, a well-established technique to investigate semantic processing. Stimuli were presented with a short SOA of 200 ms as subjects performed a lexical decision task during fMRI measurement. Seven experimental conditions were compared: positive/negative/neutral related, positive/negative/neutral unrelated, nonwords (all words were nouns). Behavioral data revealed a valence specific semantic priming effect (i.e., unrelated > related) only for neutral and positive related word pairs. On a neural level, the comparison of emotional over neutral relations showed activation in left anterior medial frontal cortex, superior frontal gyrus, and posterior cingulate. Interactions for the different relations were located in left anterior part of the medial frontal cortex, cingulate regions, and right hippocampus (positive > neutral + negative) and left posterior part of medial frontal cortex (negative > neutral + positive). The results showed that emotional information have an influence on semantic association processes. While positive and neutral information seem to share a semantic network, negative relations might induce compensatory mechanisms that inhibit the spread of activation between related concepts. The neural correlates highlighted a distributed neural network, primarily involving attention, memory and emotion related processing areas in medial fronto-parietal cortices. The differentiation between anterior (positive) and posterior part (negative) of the medial frontal cortex was linked to the type of affective manipulation with more cognitive demands being involved in the automatic processing of negative information.
Using a dual-task methodology we examined the interaction of perceiving and producing facial expressions. In one task, participants were asked to produce a smile or a frown (Task 2) in response to a tone stimulus. This auditory-facial task was embedded in a dual-task context, where the other task (Task 1) required a manual response to visual face stimuli (visual-manual task). These face stimuli showed facial expressions that were either compatible or incompatible to the to-be-produced facial expression. Both reaction times and error rates (measured by facial electromyography) revealed a robust stimulus-response compatibility effect across tasks, suggesting that perceived social actions automatically activate corresponding actions even if perceived and produced actions belong to different tasks. The dual-task nature of this compatibility effect further testifies that encoding of facial expressions is highly automatic.
Autism spectrum disorders (ASD) are pervasive developmental disorders with characteristic core symptoms such as impairments in social interaction, deviance in communication, repetitive and stereotyped behavior, and impaired motor skills. Anomalies of brain structure have repeatedly been hypothesized to play a major role in the etiopathogenesis of the disorder. Our objective was to perform unbiased meta-analysis on brain structure changes as reported in the current ASD literature. We thus conducted a comprehensive search for morphometric studies by Pubmed query and literature review. We used a revised version of the activation likelihood estimation (ALE) approach for coordinate-based meta-analysis of neuroimaging results. Probabilistic cytoarchitectonic maps were applied to compare the localization of the obtained significant effects to histological areas. Each of the significant ALE clusters was analyzed separately for age effects on gray and white matter density changes. We found six significant clusters of convergence indicating disturbances in the brain structure of ASD patients, including the lateral occipital lobe, the pericentral region, the medial temporal lobe, the basal ganglia, and proximate to the right parietal operculum. Our study provides the first quantitative summary of brain structure changes reported in literature on autism spectrum disorders. In contrast to the rather small sample sizes of the original studies, our meta-analysis encompasses data of 277 ASD patients and 303 healthy controls. This unbiased summary provided evidence for consistent structural abnormalities in spite of heterogeneous diagnostic criteria and voxel-based morphometry (VBM) methodology, but also hinted at a dependency of VBM findings on the age of the patients.
One well-investigated division of attentional processes focuses on alerting, orienting and executive control, which can be assessed applying the attentional network test (ANT). The goal of the present study was to add further knowledge about the temporal dynamics of relevant neural correlates. As a right hemispheric dominance for alerting and orienting has previously been reported for intrinsic but not for phasic alertness, we additionally addressed a potential impact of this lateralization of attention by employing a lateralized version of the ANT, capturing phasic alertness processes. Sixteen healthy subjects underwent event-related functional magnetic resonance imaging (fMRI) while performing the ANT. Analyses of BOLD magnitude replicated the engagement of a fronto-parietal network in the attentional subsystems. The amplitudes of the attentional contrasts interacted with visual field presentation in the sense that the thalamus revealed a greater involvement for spatially cued items presented in the left visual field. Comparisons of BOLD latencies in visual cortices, first, verified faster BOLD responses following contra-lateral stimulus presentation. Second and more importantly, we identified attention-modulated activation in secondary visual and anterior cingulate cortices. Results are discussed in terms of bottom-up and lateralization processes. Although intrinsic and phasic alertness are distinct cognitive processes, we propose that neural substrates of intrinsic alertness may be accessed by phasic alertness provided that the attention-dominant (i.e., the right) hemisphere is activated directly by a warning stimulus.
Emotional processing is influenced by cognitive processes and vice versa, indicating a profound interaction of these domains. The investigation of the neural mechanisms underlying this interaction is not only highly relevant for understanding the organization of human brain function. Rather, it may also help in understanding dysregulated emotions in affective disorders and in elucidating the neurobiology of cognitive behavioural therapy (e.g. in borderline personality disorder), which aims at modulating dysfunctional emotion processes by cognitive techniques, such as restructuring. In the majority of earlier studies investigating the interaction of emotions and cognition, the main focus has been on the investigation of the effects of emotional stimuli or, more general, emotional processing, e.g. instituted by emotional material that needed to be processed, on cognitive performance and neural activation patterns. Here we pursued the opposite approach and investigated the modulation of implicit processing of emotional stimuli by cognitive demands using an event-related functional magnetic resonance imaging--study on a motor short-term memory paradigm with emotional interferences. Subjects were visually presented a finger-sequence consisting either of four (easy condition) or six (difficult condition) items, which they had to memorize. After a short pause positive, negative or neutral International affective picture system pictures or a green dot (as control condition) were presented. Subjects were instructed to reproduce the memorized sequence manually as soon as the picture disappeared. Analysis showed that with increasing cognitive demand (long relative to short sequences), neural responses to emotional pictures were significantly reduced in amygdala and orbitofrontal cortex. In contrast, the more difficult task evoked stronger activation in a widespread frontoparietal network. As stimuli were task-relevant go-cues and hence had to be processed perceptually, we would interpret this as a specific attenuation of affective responses by concurrent cognitive processing--potentially reflecting a relocation of resources mediated by the frontoparietal network.
The cholinergic system is essential in mediating cognitive processes. Although there has been extensive research regarding cholinergic receptor subsystems, the specific contribution of the muscarinic and nicotinic receptor system to cognitive processes still has not been sufficiently explored. In the present study, we examined the selective contribution of muscarinic and nicotinic antagonism to cognitive performance in healthy human subjects. A single-blind, double-dummy, time-elapsed, repeated measures cross-over design was used on 15 healthy males. Subjects completed a neuropsychological test battery assessing a wide range of cognitive domains after 0.4 mg scopolamine (intravenous), 0.2 mg/kg mecamylamine (max. 15 mg; oral) or placebo. Subjects were tested under three conditions: placebo/placebo (PP), scopolamine/placebo (SP) and mecamylamine/placebo (MP). Results show that scopolamine significantly impaired the free recall and recognition performance in the verbal learning test. No other cognitive domain was affected, neither by scopolamine nor by mecamylamine. In line with the existing literature, antagonism of muscarinic receptors resulted in specific cognitive impairments, predominantly memory performance.
The goal of the current studies was to examine perception-action interactions in a socially relevant domain. Social interactions are based on a mutual understanding of the emotions and actions of others. We assume that the perception of emotional actions also stimulates a parallel action preparation in the perceiver, underlining the common coding theory. We report two experiments aimed to examine whether the perception of socially relevant facial actions (e.g., happy vs. angry facial expressions) interact with the execution of such actions. More specifically, we use a stimulus-response compatibility paradigm, in which subjects responded to the gender of a face by either smiling or frowning while ignoring the fact that the presented face is also randomly either smiling or frowning. We measured reaction time (RT) as onset latency on the two large muscle groups used for smiling (zygomaticus major) and frowning (corrugator supercilii) using electromyography. Experiment 1 showed that on compatible trials, in which perceived facial expression and actually produced facial expression matched, RTs were shorter than on incompatible trials. Experiment 2 used pre-instructed (i.e., blocked) responses and replicated the compatibility effect, suggesting that the effect is functionally located not in response selection but in response initiation or execution. We discuss these results in relation to cognitive mechanisms of common coding of perception and action and to the human mirror neuron system.
Emotions are often encountered in a multimodal fashion. Consequently, contextual framing by other modalities can alter the way that an emotional facial expression is perceived and lead to emotional conflict. Whole brain fMRI data was collected when 35 healthy subjects judged emotional expressions in faces while concurrently being exposed to emotional (scream, laughter) or neutral (yawning) sounds. The behavioral results showed that subjects rated fearful and neutral faces as being more fearful when accompanied by screams than compared to yawns (and laughs for fearful faces). Moreover, the imaging data revealed that incongruence of emotional valence between faces and sounds led to increased activation in the middle cingulate cortex, right superior frontal cortex, right supplementary motor area as well as the right temporoparietal junction. Against expectations no incongruence effects could be found in the amygdala. Further analyses revealed that, independent of emotional valence congruency, the left amygdala was consistently activated when the information from both modalities was emotional. If a neutral stimulus was present in one modality and emotional in the other, activation in the left amygdala was significantly attenuated. These results indicate that incongruence of emotional valence in audiovisual integration activates a cingulate-fronto-parietal network involved in conflict monitoring and resolution. Furthermore in audiovisual pairing amygdala responses seem to signal also the absence of any neutral feature rather than only the presence of an emotionally charged one.
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.
The current study aimed to investigate predictive markers for acute symptoms of depression and mania following deep brain stimulation (DBS) surgery of the subthalamic nucleus for the treatment of motor symptoms in Parkinsons disease (PD). Fourteen patients with PD (7 males) were included in a prospective longitudinal study. Neuropsychological tests, psychopathology scales and tests of motor functions were administered at several time points prior to and after neurosurgery. Pre-existing psychopathological and motor symptoms predicted postoperative affective side effects of DBS surgery. As these can easily be assessed, they should be considered along with other selection criteria for DBS surgery.
Tourettes syndrome is characterised by motor and vocal tics as well as a high level of impulsivity and emotional dysregulation. Neuroimaging studies point to structural changes of the basal ganglia, prefrontal cortex and parts of the limbic system. However, there is no link between behavioural symptoms and the structural changes in the amygdala. One aspect of daily social interaction is the perception of emotional facial expressions, closely linked to amgydala function.
The aim of the present study was to assess the effect of age on cerebral correlates of olfactory induced negative emotions. We investigated 15 healthy women (aged 21-47) in a functional MRI (fMRI) study during passive smelling of one negative odor (rotten yeast) and two control conditions presenting a neutral odor (vanilla) and odorless ambient air. Besides odor-specific differences in ratings of valence (yeast less pleasant than vanilla and air), intensity (yeast more intense than vanilla and air), and arousal (yeast more arousing than vanilla and air), self-ratings verified the intended mood induction effect: subjects experienced more disgust during yeast stimulation compared to ambient air and vanilla. Along with the superior temporal cortex, medial, and lateral orbitofrontal activations were found to discriminate between negative and neutral olfactory stimulation (yeast and vanilla) directly. Activations of the dorsolateral prefrontal cortex and the caudate were correlated with age and showed stronger valence-related responses (yeast vs. vanilla) in younger compared to older women. Stronger BOLD signals within the anterior cingulate gyrus, insula and motor areas were found during negative compared to neutral stimulation and are considered to represent an attempt to down-regulate the strong emotional experience and the organisms preparation for withdrawal, respectively. Our results stress the role of orbitofrontal and superior temporal brain regions in odor-related valence coding and stress the necessity to consider age as a modulating factor for further studies, even in relatively young samples.
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.
Patients with schizophrenia frequently have deficits in social cognition, and difficulties in the discrimination of emotional facial expressions have been discussed as an important contributing factor. We investigated whether this impairment is aggravated by difficulties relating the observed facial expression to contextual information, as is often provided by emotionally valenced crossmodal stimulation.
Emotional faces communicate both the emotional state and behavioral intentions of an individual. They also activate behavioral tendencies in the perceiver, namely approach or avoidance. Here, we compared more automatic motor to more conscious rating responses to happy, sad, angry, and disgusted faces in a healthy student sample. Happiness was associated with approach and anger with avoidance. However, behavioral tendencies in response to sadness and disgust were more complex. Sadness produced automatic approach but conscious withdrawal, probably influenced by interpersonal relations or personality. Disgust elicited withdrawal in the rating task, whereas no significant tendency emerged in the joystick task, probably driven by expression style. Based on our results, it is highly relevant to further explore actual reactions to emotional expressions and to differentiate between automatic and controlled processes because emotional faces are used in various kinds of studies. Moreover, our results highlight the importance of gender of poser effects when applying emotional expressions as stimuli.
The "self-reference effect" describes better memory for material someone has related to ones 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.
Facilitation of emotional face recognition is an established phenomenon for audiovisual crossmodal stimulation, but not for other sensory modalities. The present study used a crossmodal priming task to identify brain systems controlling olfactory-visual interactions during emotion processing. BOLD fMRI was acquired for 44 healthy subjects during an emotional face discrimination task preceded by an emotionally valenced odorant. Behavioral performance showed that recognition of disgusted faces was improved by the presentation of an olfactory stimulus irrespective of its emotional valence. No such facilitation was seen for other facial expressions. The neuroimaging data showed a selective default network responsivity to emotional faces which was modulated by odor condition. Among disgust faces, hypoactivations during trials preceded by odorants indicated the presence of priming effects. Consistent with studies investigating the brain systems associated with audiovisual emotional integration, activity modulations in clusters in fusiform gyrus, middle frontal and middle cingulate gyrus corresponded to the observed behavioral facilitation. Our study further shows modulation of signal in the anterior insula during trials combining negatively valenced odor and disgusted faces, suggesting a modality-specific mechanism for integration of the disgust response and olfaction. These results indicate the presence of a central network with modality-specific and -unspecific components modulating emotional face recognition.
Emotional facial expressions are the most salient cues in social life. Successful social interaction is based on correct recognition, interpretation and appropriate reaction to these cues. However, social skill deficits are among the most debilitating symptoms of depression, leading to social withdrawal and aggravating the disorder in various domains. We used an implicit joystick task to measure automatic behavioral tendencies in response to evoked facial expressions (anger, fear, sadness, happiness and neutral). Additionally, we implemented a rating procedure to assess explicit approach and avoidance reactions to these social stimuli. Our sample consisted of 24 depressed patients and 24 healthy controls. Data analysis indicated that depressed patients appear to understand the expression depicted on the emotional faces but react differently to these social cues. Female patients displayed stronger avoidance tendencies in the explicit condition whereas social withdrawal was less pronounced in the implicit condition. Our data suggest that a cognitive bias negatively influences the unimpaired automatic reactions to emotional expressions in depressed patients, and this bias may result in the characteristic social withdrawal.
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.
Recently, a standardized program for training of affect recognition (TAR) was developed which has demonstrated efficacy and specificity with respect to behavioral performance. The effects of the TAR on the cerebral correlates were evaluated using repeated fMRI event-related measurements in a group of schizophrenia patients (n=10) before and after TAR treatment six weeks apart. A second patient group without training (n=10, treatment as usual, TAU) as well as healthy subjects (n=10) were investigated at equivalent time points. Schizophrenia patients were shown to be differentially impaired in the identification of the emotional aspects of facial expressions (but not age discrimination) when compared with healthy participants. A specific improvement in the increased number of correct identifications was observed in trained patients only. In parallel, an increase in activation was noted in the left middle and superior occipital lobe, the right inferior and superior parietal cortex, and the inferior frontal cortex bilaterally in TAR patients compared to the TAU group. These activation changes in TAR patients correlated with their behavioral improvement, further corroborating the positive effect of training. Specific training effects are seen to correspond with cerebral effects, probably reflecting a more efficient use of attentional, perceptual, or cognitive strategies.
Acetylcholine plays a major role in mediating attention processes. We investigated the muscarinic antagonist effect of scopolamine on functional neuro-anatomy of attention and cognition. We assessed 12 healthy volunteers while performing the Attention Network Task on 0.4 mg scopolamine and placebo in a single-blind randomized trial in a 1.5 T magnetic resonance scanner. Neurocognitive measures included verbal learning, verbal memory, verbal fluency, trail making, digit span, a continuous performance task and a planning task (Tower of London). When compared to placebo, scopolamine increased reaction times for conflicting stimulus processing, together with decreasing brain activation in the anterior cingulate cortex (a brain region involved in conflict processing) suggestive of a muscarinic antagonist effect on executive control of attention. Contrary to the notion of a predominantly right-hemispheric lateralization of cognitive processes associated with orienting attention, scopolamine reduced brain activity in left superior and left middle frontal brain areas. Our neuropsychological test data revealed a selective effect of scopolamine on verbal learning and memory while other cognitive domains, such as planning and working memory, were unaffected. These findings are consistent with muscarinic modulation of dopaminergic neurotransmission in frontal attention networks when processing conflicting information.
Cholinergic neurotransmission has been implicated in memory and attention. We investigated the effect of the non-competitive nicotinic antagonist mecamylamine on three components of attention processes (i.e. alerting, orienting and executive control) in 12 healthy male subjects whilst performing the Attention Network Task (ANT) in a magnetic resonance imaging (MRI) scanner. Participants received 15 mg mecamylamine in a single blind and placebo- controlled randomized procedure 90 min prior to obtaining functional MRI data. Our results confirm previous reports of beneficial effects of cueing (alerting and orienting) and detrimental effects of conflict (executive control) on reaction times when performing the ANT. The functional MRI data confirmed distinct neural networks associated with each of the three attention components. Alerting was associated with increased left temporal lobe activation while orienting increased bilateral prefrontal, right precuneus and left caudate activation. Executive control activated anterior cingulate and precuneus. Mecamylamine slowed overall response time and down-regulated brain activation associated with orienting and to some extent brain activation associated with executive control when compared to placebo. These findings are consistent with nicotinic modulation of orienting attention by cueing and executive control when responding to conflicting information. The latter nicotine antagonist effect may be mediated via cholinergic modulation of dopamine neurotransmission in mesolimbic pathways.
The ability to recognize emotions in facial expressions relies on an extensive neural network with the amygdala as the key node as has typically been demonstrated for the processing of fearful stimuli. A sufficient characterization of the factors influencing and modulating amygdala function, however, has not been reached now. Due to lacking or diverging results on its involvement in recognizing all or only certain negative emotions, the influence of gender or ethnicity is still under debate. This high-resolution fMRI study addresses some of the relevant parameters, such as emotional valence, gender and poser ethnicity on amygdala activation during facial emotion recognition in 50 Caucasian subjects. Stimuli were color photographs of emotional Caucasian and African American faces.
Empathy is a multidimensional construct composed of several components such as emotion recognition, emotional perspective taking and affective responsiveness. Patients with schizophrenia demonstrate deficits in several domains of emotion processing and perspective taking, thus suggesting a dysfunctional emotional competence. We assessed empathic abilities via three paradigms measuring emotion recognition, perspective taking and affective responsiveness as well as self-report empathy questionnaires in 24 (12 females, 12 males) schizophrenia patients meeting the DSM-IV criteria for schizophrenia and 24 matched healthy volunteers. Patients were recruited from the Department of Psychiatry and Psychotherapy, RWTH Aachen University and healthy volunteers were recruited via advertisement. Groups were matched for age, gender and parental education. Data analysis indicates a significant empathic deficit in patients, reflected in worse performance in all three domains. This deficit was only partly reflected in the self-report empathy questionnaires. Comparing the different tasks, emotional perspective taking was the most difficult task for all subjects and symptomatology worsened affective responsiveness. Schizophrenia patients not only struggle to correctly identify emotions, but also have difficulties in spontaneously simulating another persons subjective world (perspective taking) and might not be able to respond adequately in terms of their own emotional experience (affective responsiveness), which are not caused by emotion perception deficits. The results suggest that all domains of empathy are affected in schizophrenia and have to be addressed independently in behavioral therapies, thereby offering a possibility to improve socio-occupational life.
Cultural differences in emotion recognition performance have frequently been reported, whereby duration of stay in a foreign culture seems to be a crucial factor. Furthermore, cultural aspects influence the neural correlates of face and emotion processing thereby also affecting the response of the amygdala. Here, the exposure to a foreign culture and its influence on the cerebral correlates of facial emotion recognition were examined in 24 Asian and 24 age-matched European males. Subjects performed an explicit emotion recognition task and were imaged with a 3 T MR-scanner. Results demonstrate a significant cultural influence on the specific recognition of disgust and anger, with higher accuracy among the Europeans, while the functional data indicate generally elevated amygdala activation in Asians compared to Europeans. Moreover, a significant inverse correlation between duration of stay and amygdala response emerged, with stronger activation in those subjects with shorter duration of stay in Europe. The observed amygdala hyperactivation in Asians may reflect novelty aspects but might also be associated with greater effort and motivation in immigrants, thus it possibly reflects one neural correlate of the "alien-effect". We conclude that exposure to a foreign culture and duration of stay affect the behavioral and neural response to facial expressions of emotions.
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.
The Neuregulin (NRG1) gene has been associated with schizophrenia, but its functional implications are largely unknown. Our aim was to assess differential brain activation between patients carrying an at-risk allele on the Neuregulin 1 gene and patients without this genetic risk. Neural signal changes between 14 first episode schizophrenia patients with the at risk allele (SNP8NRG221533) from the Icelandic core haplotype and 14 without were measured with fMRI during a working memory task. Patients without the at risk allele showed greater activations (P < 0.05; corrected) in the left hippocampus, precuneus and cerebellum, as well as the right anterior cingulate. Brain regions previously associated with the pathology of Schizophrenia are differentially affected in those with a genetic at risk status in the NRG1 gene. Heterogeneity of structural and functional measures within patients characterized by clinical phenotypes may be in part due to this genetic variation.
Olfactory perception is characterized by interpersonal variability. Although gender has been identified as a potential influencing factor, currently little is known about its effect on perceived hedonicity of individual odorants. This study assessed gender differences in emotional appraisal of 3 odorants (eugenol, vanillin, and hydrogen sulfide [H(2)S]), presented to 25 healthy subjects (13 males, 12 females) in a blocked design. Standardized scales rating valence and judgments of emotional experience were used for stimulus evaluation. Results indicate ambiguous pleasantness ratings for eugenol as well as stronger responses to vanillin odorant in female subjects; furthermore, in emotional experience ratings, the effect of eugenol was found to be gender dependent, evoking more positive and less negative emotions in female subjects than in males. The gender dependence of the mood response to eugenol necessitates reconsideration of this odorant as a reliable gender independent olfactory stimulus for studies on olfaction and emotion.
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.
In everyday life causal attribution is important in order to structure the complex world, provide explanations for events and to understand why our environment interacts with us in a particular way. This study used functional magnetic resonance imaging (fMRI) in 30 healthy subjects to separate the neural correlates of self vs. external responsibility for social events and explore the neural basis of self-serving attributions (internal attributions of positive events and external attributions of negative events). We presented short sentences describing positive and negative social events and asked participants to imagine the event, to decide the main cause and assign it to one of the categories (internal vs. external). FMRI data were analyzed using a 2 x 2 factorial design with the factors emotional valence and attribution. Internal compared to external attribution revealed activations along the right temporoparietal junction (TPJ). The reverse contrast showed a left lateralized network mainly involving the TPJ, the precuneus and the superior/medial frontal gyrus. These results confirmed the involvement of a fronto-temporoparietal network in differentiating self and external responsibility. Analysis of the self-serving bias yielded activation in the dorsal anterior cingulate and in the dorsal striatum, suggesting a rewarding value of these attributions.
Neuroimaging studies have documented modulation of the activity of the amygdala - a key node in the neural network underlying emotion perception and processing, and one that has also been associated with regulating aggression - by exogenous testosterone. However, results on the impact of normal range testosterone levels on explicit emotion recognition as a prerequisite for social interaction and amygdala activation in healthy young males are missing. Hence, we performed functional MRI at 3T in a group of 21 healthy males during explicit emotion recognition with a protocol specifically optimized to reliably detect amygdala activation. We observed similar amygdala activation to all emotions presented without any effect of gender of poser or laterality. Reaction times to fearful male faces were found negatively correlated to testosterone concentration, while no significant effects emerged for other emotions and neutral expressions. Correlation analyses revealed a significant positive association between testosterone levels and amygdala response to fearful and angry facial expressions, but not to other expressions. Hence, our results demonstrate that testosterone levels affect amygdala activation and also behavioral responses particularly to threat-related emotions in healthy young males. We conclude that these findings add to our understanding of emotion processing and its modulation by neuroendocrine factors.
Cognitive task demands in one sensory modality (T1) can have beneficial effects on a secondary task (T2) in a different modality, due to reduced top-down control needed to inhibit the secondary task, as well as crossmodal spread of attention. This contrasts findings of cognitive load compromising a secondary modalitys processing. We manipulated cognitive load within one modality (visual) and studied the consequences of cognitive demands on secondary (auditory) processing. 15 healthy participants underwent a simultaneous EEG-fMRI experiment. Data from 8 participants were obtained outside the scanner for validation purposes. The primary task (T1) was to respond to a visual working memory (WM) task with four conditions, while the secondary task (T2) consisted of an auditory oddball stream, which participants were asked to ignore. The fMRI results revealed fronto-parietal WM network activations in response to T1 task manipulation. This was accompanied by significantly higher reaction times and lower hit rates with increasing task difficulty which confirmed successful manipulation of WM load. Amplitudes of auditory evoked potentials, representing fundamental auditory processing showed a continuous augmentation which demonstrated a systematic relation to cross-modal cognitive load. With increasing WM load, primary auditory cortices were increasingly deactivated while psychophysiological interaction results suggested the emergence of auditory cortices connectivity with visual WM regions. These results suggest differential effects of crossmodal attention on fundamental auditory processing. We suggest a continuous allocation of resources to brain regions processing primary tasks when challenging the central executive under high cognitive load.
Empathy is a rather elaborated human ability and several recent studies highlight significant impairments in patients suffering from psychiatric disorders, such as schizophrenia, bipolar disorder or major depression. Therefore, the present study aimed at comparing behavioral empathy performance in schizophrenia, bipolar and depressed patients with healthy controls. All subjects performed three tasks tapping the core components of empathy: emotion recognition, emotional perspective taking and affective responsiveness. Groups were matched for age, gender, and verbal intelligence. Data analysis revealed three main findings: First, schizophrenia patients showed the strongest impairment in empathic performance followed by bipolar patients while depressed patients performed similar to controls in most tasks, except for affective responsiveness. Second, a significant association between clinical characteristics and empathy performance was only apparent in depression, indicating worse affective responsiveness with stronger symptom severity and longer duration of illness. Third, self-report data indicate that particularly bipolar patients describe themselves as less empathic, reporting less empathic concern and less perspective taking. Taken together, this study constitutes the first approach to directly compare specificity of empathic deficits in severe psychiatric disorders. Our results suggest disorder-specific impairments in emotional competencies that enable better characterization of the patient groups investigated and indicate different psychotherapeutic interventions.
Evidence has accumulated that emotion recognition performance varies with menstrual cycle phase. However, according to some empathy models, facial affect recognition constitutes only one component of empathic behavior, besides emotional perspective taking and affective responsiveness. It remains unclear whether menstrual cycle phase and thus estradiol and progesterone levels are also associated with the two other empathy constructs. Therefore, we investigated 40 healthy right-handed females, 20 during their follicular phase and 20 during their midluteal phase and compared their performance in three tasks tapping the empathic components as well as self-report data. Salivary hormone levels were obtained and correlated with performance parameters. Subjects were matched for age and education and did not differ in neuropsychological function. Analysis of empathy performance revealed a significant effect of phase in emotion recognition, showing higher accuracy in the follicular group. Regarding affective responsiveness, we observed a significant difference in reaction times, with faster responses for sad and angry stimuli in the midluteal group. No significant group difference emerged for emotional perspective taking. Furthermore, significant correlations between progesterone levels and emotion recognition accuracy and affective responsiveness emerged only in the luteal group. However, groups did not differ in self-reported empathy. Our results indicate that menstrual cycle phase and thus ovarian hormone concentration are differentially related to empathic behavior, particularly emotion recognition and responsiveness to negative situations, with progesterone covarying with both in the luteal phase.
According to the aberrant-salience hypothesis, attribution of motivational salience is severely disrupted in patients with schizophrenia. To provide a translational approach for investigating underlying mechanisms, neural correlates of salience attribution were examined in normal mice and in a MK-801 model of schizophrenia. Electrophysiological responses to standard and deviant tones were assessed in the medial prefrontal cortex (mPFC) using an auditory oddball paradigm. Motivational salience was induced by aversive conditioning to the deviant tone. Analysis of the auditory evoked potential (AEP) showed selective modulation of the late frontal negativity (LFN) by motivational salience, which persisted throughout a 4-week delay. MK-801, an N-methyl-D-aspartic acid receptor antagonist, abolished this differential response to motivational salience in conditioned mice. In contrast, a pronounced LFN response was observed towards the deviant, ie, perceptually salient tone, in nonconditioned mice. The finding of a selective modulation of a late frontal slow wave suggests increased top-down processing and emotional evaluation of motivationally salient stimuli. In particular, the LFN is discussed as the mouse analog to the human stimulus preceding negativity, which reflects preparatory processes in anticipation of reward or punishment. MK-801 led to a disruption of the normal response in conditioned and nonconditioned mice, including an aberrantly increased LFN in nonconditioned mice. This pattern of false-negative and false-positive responses suggests a degradation of salience attribution, which points to mPFC responses to be relevant for translational research on cognitive alterations in schizophrenia.
Insights from both lesion and neuroimaging studies increasingly substantiate the view that the human cerebellum not only serves motor control but also supports various cognitive processes. Higher cognitive functions like working memory or executive control have been associated with the phylogenetically younger parts of the cerebellum, crus I and crus II. Functional connectivity studies corroborate this notion as activation of the cerebellum correlates with activity in numerous areas of the cerebral cortex. Moreover, these cerebrocerebellar loops were shown to be topographically organized. We used an attention-to-motion paradigm to elaborate on the effective connectivity of cerebellar crus I during visual attention. Psychophysiological interaction analyses demonstrated enhanced connectivity of the cerebellum--during attention--with dorsal visual stream regions including posterior parietal cortex (PPC) and left secondary visual cortex (V5). Dynamic causal modeling revealed a modulation of the connections from V5 to PPC and from crus I to V5 by attention. Remarkably, the influence which V5 exerted on PPC was reduced during attention, resulting in a suppression of the sensitivity of PPC to bottom-up information. Moreover, the sensitivity of V5 populations to inputs from crus I was increased under attention. This might underscore the presumed role of the cerebellum as a state estimator that provides hierarchically lower regions (V5) with top-down predictions, which in turn might be based on endogenous inputs from PPC to the cerebellum. These results are in line with formulations of attention in predictive coding, where attention increases the precision or sensitivity of hierarchically lower neuronal populations that may encode prediction error.
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.
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