The plasticity of social emotions

Social emotions such as empathy or compassion greatly facilitate our interactions with others. Despite the importance of social emotions, scientific studies have only recently revealed functional neural plasticity associated with the training of such emotions. Using the framework of two antagonistic neural systems, the threat and social disconnection system on the one hand, and the reward and social connection system on the other, this article describes how training compassion and empathy can change the functioning of these systems in a targeted manner. Whereas excessive empathic sharing of suffering can increase negative feelings and activations in the insula and anterior cingulate cortex (corresponding to the threat and social disconnection system), compassion training can strengthen positive affect and neural activations in the medial orbitofrontal cortex and striatum (corresponding to the reward and social connection system). These neuroimaging findings are complemented by results from behavioral studies showing that compassion is linked to helping and forgiveness behavior, whereas empathic distress not only decreases helping behavior, but is even associated with increased aggressive behavior. Taken together, these data provide encouraging evidence for the plasticity of adaptive social emotions with wide-ranging implications for basic science and applied settings.     

Mindfulness meditation regulates anterior insula activity during empathy for social pain

Mindfulness has been shown to reduce stress, promote health, and well‐being, as well as to increase compassionate behavior toward others. It reduces distress to one's own painful experiences, going along with altered neural responses, by enhancing self‐regulatory processes and decreasing emotional reactivity. In order to investigate if mindfulness similarly reduces distress and neural activations associated with empathy for others' socially painful experiences, which might in the following more strongly motivate prosocial behavior, the present study compared trait, and state effects of long‐term mindfulness meditation (LTM) practice. To do so we acquired behavioral data and neural activity measures using functional magnetic resonance imaging (fMRI) during an empathy for social pain task while manipulating the meditation state between two groups of LTM practitioners that were matched with a control group. The results show increased activations of the anterior insula (AI) and anterior cingulate cortex (ACC) as well as the medial prefrontal cortex and temporal pole when sharing others' social suffering, both in LTM practitioners and controls. However, in LTM practitioners, who practiced mindfulness meditation just prior to observing others' social pain, left AI activation was lower and the strength of AI activation following the mindfulness meditation was negatively associated with trait compassion in LTM practitioners. The findings suggest that current mindfulness meditation could provide an adaptive mechanism in coping with distress due to the empathic sharing of others' suffering, thereby possibly enabling compassionate behavior. Hum Brain Mapp 38:4034–4046, 2017. © 2017 Wiley Periodicals, Inc.     

Characterization of empathy deficits following prefrontal brain damage: the role of the right ventromedial prefrontal cortex

Impaired empathic response has been described in patients following brain injury, suggesting that empathy may be a fundamental aspect of the social behavior disturbed by brain damage. However, the neuroanatomical basis of impaired empathy has not been studied in detail. The empathic response of patients with localized lesions in the prefrontal cortex (n = 25) was compared to responses of patients with posterior (n = 17) and healthy control subjects (n = 19). To examine the cognitive processes that underlie the empathic ability, the relationships between empathy scores and the performance on tasks that assess processes of cognitive flexibility, affect recognition, and theory of mind (TOM) were also examined. Patients with prefrontal lesions, particularly when their damage included the ventromedial prefrontal cortex, were significantly impaired in empathy as compared to patients with posterior lesions and healthy controls. However, among patients with posterior lesions, those with damage to the right hemisphere were impaired, whereas those with left posterior lesions displayed empathy levels similar to healthy controls. Seven of nine patients with the most profound empathy deficit had a right ventromedial lesion. A differential pattern regarding the relationships between empathy and cognitive performance was also found: Whereas among patients with dorsolateral prefrontal damage empathy was related to cognitive flexibility but not to TOM and affect recognition, empathy scores in patients with ventromedial lesions were related to TOM but not to cognitive flexibility. Our findings suggest that prefrontal structures play an important part in a network mediating the empathic response and specifically that the right ventromedial cortex has a unique role in integrating cognition and affect to produce the empathic response.     

Age-dependent changes in the neural substrates of empathy in autism spectrum disorder

In typical development, empathic abilities continue to refine during adolescence and early adulthood. Children and adolescents with autism spectrum disorders (ASD) show deficits in empathy, whereas adults with ASD may have developed compensatory strategies. We aimed at comparing developmental trajectories in the neural mechanisms underlying empathy in individuals with ASD and typically developing control (TDC) subjects. Using an explicit empathizing paradigm and functional magnetic resonance imaging, 27 participants with ASD and 27 TDC aged 12–31 years were investigated. Participants were asked to empathize with emotional faces and to either infer the face’s emotional state (other-task) or to judge their own emotional response (self-task). Differential age-dependent changes were evident during the self-task in the right dorsolateral prefrontal cortex, right medial prefrontal cortex, right inferior parietal cortex, right anterior insula and occipital cortex. Age-dependent decreases in neural activation in TDC were paralleled by either increasing or unchanged age-dependent activation in ASD. These data suggest ASD-associated deviations in the developmental trajectories of self-related processing during empathizing. In TDC, age-dependent modulations of brain areas may reflect the ‘fine-tuning’ of cortical networks by reduction of task-unspecific brain activity. Increased age-related activation in individuals with ASD may indicate the development of compensatory mechanisms.     

Emotional contagion for pain is intact in autism spectrum disorders

Perceiving others in pain generally leads to empathic concern, consisting of both emotional and cognitive processes. Empathy deficits have been considered as an element contributing to social difficulties in individuals with autism spectrum disorders (ASD). Here, we used functional magnetic resonance imaging and short video clips of facial expressions of people experiencing pain to examine the neural substrates underlying the spontaneous empathic response to pain in autism. Thirty-eight adolescents and adults of normal intelligence diagnosed with ASD and 35 matched controls participated in the study. In contrast to general assumptions, we found no significant differences in brain activation between ASD individuals and controls during the perception of pain experienced by others. Both groups showed similar levels of activation in areas associated with pain sharing, evidencing the presence of emotional empathy and emotional contagion in participants with autism as well as in controls. Differences between groups could be observed at a more liberal statistical threshold, and revealed increased activations in areas involved in cognitive reappraisal in ASD participants compared with controls. Scores of emotional empathy were positively correlated with brain activation in areas involved in embodiment of pain in ASD group only. Our findings show that simulation mechanisms involved in emotional empathy are preserved in high-functioning individuals with autism, and suggest that increased reappraisal may have a role in their apparent lack of caring behavior.     

Empathic arousal and social understanding in individuals with autism: evidence from fMRI and ERP measurements

Lack of empathy is a hallmark of social impairments in individuals with autism spectrum disorder (ASD). However, the concept empathy encompasses several socio-emotional and behavioral components underpinned by interacting brain circuits. This study examined empathic arousal and social understanding in individuals with ASD and matched controls by combining pressure pain thresholds (PPT) with functional magnetic resonance imaging (study 1) and electroencephalography/event-related potentials and eye-tracking responses (study 2) to empathy-eliciting stimuli depicting physical bodily injuries. Results indicate that participants with ASD had lower PPT than controls. When viewing body parts being accidentally injured, increased hemodynamic responses in the somatosensory cortex (SI/SII) but decreased responses in the anterior mid-cingulate and anterior insula as well as heightened N2 but preserved late-positive potentials (LPP) were detected in ASD participants. When viewing a person intentionally hurting another, decreased hemodynamic responses in the medial prefrontal cortex and reduced LPP were observed in the ASD group. PPT was a mediator for the SI/SII response in predicting subjective unpleasantness ratings to others’ pain. Both ASD and control groups had comparable mu suppression, indicative of typical sensorimotor resonance. The findings demonstrate that, in addition to reduced pain thresholds, individuals with ASD exhibit heightened empathic arousal but impaired social understanding when perceiving others’ distress.     

Neural substrates underlying intentional empathy

Although empathic responses to stimuli with emotional contents may occur automatically, humans are capable to intentionally empathize with other individuals. Intentional empathy for others is even possible when they do not show emotional expressions. However, little is known about the neuronal mechanisms of this intentionally controlled empathic process. To investigate the neuronal substrates underlying intentional empathy, we scanned 20 healthy Chinese subjects, using fMRI, when they tried to feel inside the emotional states of neutral or angry faces of familiar (Asian) and unfamiliar (Caucasian) models. Skin color evaluation of the same stimuli served as a control task. Compared to a baseline condition, the empathy task revealed a network of established empathy regions, including the anterior cingulate cortex, bilateral inferior frontal cortex and bilateral anterior insula. The contrast of intentional empathy vs skin color evaluation, however, revealed three regions: the bilateral inferior frontal cortex, whose hemodynamic responses were independent of perceived emotion and familiarity and the right-middle temporal gyrus, whose activity was modulated by emotion but not by familiarity. These findings extend our understanding of the role of the inferior frontal cortex and the middle temporal gyrus in empathy by demonstrating their involvement in intentional empathy.     

Risk factors for internalizing symptoms: The influence of empathy,theory of mind,and negative thinking processes

Internalizing symptoms such as elevated stress and sustained negative affect can be important warning signs for developing mental disorders. A recent theoretical framework suggests a complex interplay of empathy, theory of mind (ToM), and negative thinking processes as a crucial risk combination for internalizing symptoms. To disentangle these relationships, this study utilizes neural, behavioral, and self-report data to examine how the interplay between empathy, ToM, and negative thinking processes relates to stress and negative affect. We reanalyzed the baseline data of N = 302 healthy participants (57% female, M_age = 40.52, SD_age = 9.30) who participated in a large-scale mental training study, the ReSource project. Empathy and ToM were assessed using a validated fMRI paradigm featuring naturalistic video stimuli and via self-report. Additional self-report scales were employed to measure internalizing symptoms (perceived stress, negative affect) and negative thinking processes (rumination and self-blame). Our results revealed linear associations of self-reported ToM and empathic distress with stress and negative affect. Also, both lower and higher, compared to average, activation in the anterior insula during empathic processing and in the middle temporal gyrus during ToM performance was significantly associated with internalizing symptoms. These associations were dependent on rumination and self-blame. Our findings indicate specific risk constellations for internalizing symptoms. Especially people with lower self-reported ToM and higher empathic distress may be at risk for more internalizing symptoms. Quadratic associations of empathy- and ToM-related brain activation with internalizing symptoms depended on negative thinking processes, suggesting differential effects of cognitive and affective functioning on internalizing symptoms. Using a multi-method approach, these findings advance current research by shedding light on which complex risk combinations of cognitive and affective functioning are relevant for internalizing symptoms.     

Empathy-related differences in the anterior cingulate functional connectivity of regular cannabis users when compared to controls

It has been reported that cannabis consumption affects the anterior cingulate cortex (ACC), a structure with a central role in mediating the empathic response. In this study, we compared psychometric scores of empathy subscales, between a group of regular cannabis users (85, users) and a group of non-consumers (51, controls). We found that users have a greater Emotional Comprehension, a cognitive empathy trait involving the understanding of the “other” emotional state. Resting state functional MRI in a smaller sample (users = 46, controls = 34) allowed to identify greater functional connectivity (FC) of the ACC with the left somatomotor cortex (SMC), in users when compared to controls. These differences were also evident within the empathy core network, where users showed greater within network FC. The greater FC showed by the users is associated with emotional representational areas and empathy-related regions. In addition, the differences in psychometric scores suggest that users have more empathic comprehension. These findings suggest a potential association between cannabis use, a greater comprehension of the other's affective state and the functional brain organization of the users. However, further research is needed to explore such association, since many other factors may be at play.     

Visceromotor roots of aesthetic evaluation of pain in art: an fMRI study

Empathy for pain involves sensory and visceromotor brain regions relevant also in the first-person pain experience. Focusing on brain activations associated with vicarious experiences of pain triggered by artistic or non-artistic images, the present study aims to investigate common and distinct brain activation patterns associated with these two vicarious experiences of pain and to assess whether empathy for pain brain regions contributes to the formation of an aesthetic judgement (AJ) in non-art expert observers. Artistic and non-artistic facial expressions (painful and neutral) were shown to participants inside the scanner and then aesthetically rated in a subsequent behavioural session. Results showed that empathy for pain brain regions (i.e. bilateral insular cortex, posterior sector of the anterior cingulate cortex and the anterior portion of the middle cingulate cortex) and bilateral inferior frontal gyrus are commonly activated by artistic and non-artistic painful facial expressions. For the artistic representation of pain, the activity recorded in these regions directly correlated with participants’ AJ. Results also showed the distinct activation of a large cluster located in the posterior cingulate cortex/precuneus for non-artistic stimuli. This study suggests that non-beauty-specific mechanisms such as empathy for pain are crucial components of the aesthetic experience of artworks.     

Cognitive empathy modulates the processing of pragmatic constraints during sentence comprehension

Previous studies have shown that brain regions for mentalizing, including temporoparietal junction (TPJ) and medial prefrontal cortex (mPFC), are activated in understanding the nonliteral meaning of sentences. A different set of brain regions, including left inferior frontal gyrus (IFG), is activated for dealing with pragmatic incongruence. Here we demonstrate that individuals’ cognitive empathic ability modulates the brain activity underlying the processing of pragmatic constraints during sentence comprehension. The lian … dou … construction in Chinese (similar to English even) normally describes an event of low expectedness; it also introduces a pragmatic scale against which the likelihood of an underspecified event can be inferred. By embedding neutral or highly likely events in the construction, we created underspecified and incongruent sentences and compared both with control sentences in which events of low expectedness were described. Imaging results showed that (i) left TPJ was activated for the underspecified sentences, and the activity in mPFC correlated with individuals’ fantasizing ability and (ii) anterior cingulate cortex (ACC) was activated for the incongruent sentences, and the activity in bilateral IFG correlated with individuals’ perspective taking ability. These findings suggest that brain activations in making pragmatic inference and in dealing with pragmatic failure are modulated by different components of cognitive empathy.     

Can we predict burnout severity from empathy-related brain activity?

Empathy cultivates deeper interpersonal relationships and is important for socialization. However, frequent exposure to emotionally-demanding situations may put people at risk for burnout. Burnout has become a pervasive problem among medical professionals because occupational burnout may be highly sensitive to empathy levels. To better understand empathy-induced burnout among medical professionals, exploring the relationship between burnout severity and strength of empathy-related brain activity may be key. However, to our knowledge, this relationship has not yet been explored. We studied the relationship between self-reported burnout severity scores and psychological measures of empathic disposition, emotional dissonance and alexithymia in medical professionals to test two contradictory hypotheses: Burnout is explained by (1) ‘compassion fatigue'' that is, individuals become emotionally over involved; and (2) ‘emotional dissonance'' that is, a gap between felt and expressed emotion, together with reduced emotional regulation. Then, we tested whether increased or decreased empathy-related brain activity measured by fMRI was associated with burnout severity scores and psychological measures. The results showed that burnout severity of medical professionals is explained by ‘reduced'' empathy-related brain activity. Moreover, this reduced brain activity is correlated with stronger emotional dissonance and alexithymia scores and also greater empathic disposition. We speculate that reduced emotion recognition (that is, alexithymia) might potentially link with stronger emotional dissonance and greater burnout severity alongside empathy-related brain activity. In this view, greater empathic disposition in individuals with higher burnout levels might be due to greater difficulty identifying their own emotional reactions. Our study sheds new light on the ability to predict empathy-induced burnout.     

Functional magnetic resonance imaging (fMRI) item analysis of empathy and theory of mind

In contrast to conventional functional magnetic resonance imaging (fMRI) analysis across participants, item analysis allows generalizing the observed neural response patterns from a specific stimulus set to the entire population of stimuli. In the present study, we perform an item analysis on an fMRI paradigm (EmpaToM) that measures the neural correlates of empathy and Theory of Mind (ToM). The task includes a large stimulus set (240 emotional vs. neutral videos to probe empathic responding and 240 ToM or factual reasoning questions to probe ToM), which we tested in two large participant samples (N = 178, N = 130). Both, the empathy‐related network comprising anterior insula, anterior cingulate/dorsomedial prefrontal cortex, inferior frontal gyrus, and dorsal temporoparietal junction/supramarginal gyrus (TPJ) and the ToM related network including ventral TPJ, superior temporal gyrus, temporal poles, and anterior and posterior midline regions, were observed across participants and items. Regression analyses confirmed that these activations are predicted by the empathy or ToM condition of the stimuli, but not by low‐level features such as video length, number of words, syllables or syntactic complexity. The item analysis also allowed for the selection of the most effective items to create optimized stimulus sets that provide the most stable and reproducible results. Finally, reproducibility was shown in the replication of all analyses in the second participant sample. The data demonstrate (a) the generalizability of empathy and ToM related neural activity and (b) the reproducibility of the EmpaToM task and its applicability in intervention and clinical imaging studies.     

Linking brain structure and activation in anterior insula cortex to explain the trait empathy for pain

The ability to perceive, understand, and react to the feelings of others' pain is referred to as empathy for pain which is composed of two components, affective‐perceptual empathy and cognitive‐evaluative empathy. Recent reviews on the neural mechanisms of empathetic pain showed the anterior insula (AI) cortex as a core circuit for empathy. However, little is known about the modulation of brain anatomy and empathic responses by trait measures of empathy (trait empathy). Thus, we investigated whether individual variation in the personality trait of empathy is associated with individual variation in the structure of specific brain regions using voxel‐based morphometry (VBM). We further investigated the relationship between the trait empathy and the activity of the same regions using state measures of empathy for pain in a trial‐by‐trial fashion in the given situation. VBM analysis indicated a small but significant negative relationship between trait empathy and gray matter volume in the bilateral AI. Functional MRI study further demonstrated that experimentally induced activity of the bilateral AI during state empathy for pain was also correlated with trait empathy. An asymmetry exists between the right and left AI between the affective and cognitive empathy. The right AI was found to be involved in the affective‐perceptual form of empathy and the left AI was active in cognitive‐evaluative forms of empathy. The interindividual differences in trait empathy may be reflected both in the state empathy and more stable brain structure difference.     

The association between ballroom dance training and empathic concern: Behavioral and brain evidence

Dance is unique in that it is a sport and an art simultaneously. Beyond improving sensorimotor functions, dance training could benefit high‐level emotional and cognitive functions. Duo dances also confer the possibility for dancers to develop the abilities to recognize, understand, and share the thoughts and feelings of their dance partners during the long‐term dance training. To test this possibility, we collected high‐resolution structural and resting‐state functional magnetic resonance imaging (MRI) data from 43 expert‐level ballroom dancers (a model of long‐term exposure to duo dance training) and 40 age‐matched and sex‐matched nondancers, and measured their empathic ability using a self‐report trait empathy scale. We found that ballroom dancers showed higher scores of empathic concern (EC) than controls. The EC scores were positively correlated with years with dance partners but negatively correlated with the number of dance partners for ballroom dancers. These behavioral results were supported by the structural and functional MRI data. Structurally, we observed that the gray matter volumes in the subgenual anterior cingulate cortex (ACC) and EC scores were positively correlated. Functionally, the connectivity between ACC and occipital gyrus was positively correlated with both EC scores and years with dance partners. In addition, the relationship between years with dance partners and EC scores was indirect‐only mediated by the ACC‐occipital gyrus functional connectivity. Therefore, our findings provided solid evidence for the close link between long‐term ballroom dance training and empathy, which deepens our understanding of the neural mechanisms underlying this phenomenon.     

The neural components of empathy: Predicting daily prosocial behavior

Previous neuroimaging studies on empathy have not clearly identified neural systems that support the three components of empathy: affective congruence, perspective-taking, and prosocial motivation. These limitations stem from a focus on a single emotion per study, minimal variation in amount of social context provided, and lack of prosocial motivation assessment. In the current investigation, 32 participants completed a functional magnetic resonance imaging session assessing empathic responses to individuals experiencing painful, anxious, and happy events that varied in valence and amount of social context provided. They also completed a 14-day experience sampling survey that assessed real-world helping behaviors. The results demonstrate that empathy for positive and negative emotions selectively activates regions associated with positive and negative affect, respectively. In addition, the mirror system was more active during empathy for context-independent events (pain), whereas the mentalizing system was more active during empathy for context-dependent events (anxiety, happiness). Finally, the septal area, previously linked to prosocial motivation, was the only region that was commonly activated across empathy for pain, anxiety, and happiness. Septal activity during each of these empathic experiences was predictive of daily helping. These findings suggest that empathy has multiple input pathways, produces affect-congruent activations, and results in septally mediated prosocial motivation.     

Affective resonance in response to others’ emotional faces varies with affective ratings and psychopathic traits in amygdala and anterior insula

Despite extensive research on the neural basis of empathic responses for pain and disgust, there is limited data about the brain regions that underpin affective response to other people’s emotional facial expressions. Here, we addressed this question using event-related functional magnetic resonance imaging to assess neural responses to emotional faces, combined with online ratings of subjective state. When instructed to rate their own affective response to others’ faces, participants recruited anterior insula, dorsal anterior cingulate, inferior frontal gyrus, and amygdala, regions consistently implicated in studies investigating empathy for disgust and pain, as well as emotional saliency. Importantly, responses in anterior insula and amygdala were modulated by trial-by-trial variations in subjective affective responses to the emotional facial stimuli. Furthermore, overall task-elicited activations in these regions were negatively associated with psychopathic personality traits, which are characterized by low affective empathy. Our findings suggest that anterior insula and amygdala play important roles in the generation of affective internal states in response to others’ emotional cues and that attenuated function in these regions may underlie reduced empathy in individuals with high levels of psychopathic traits.     

Sleep quality and its association with the insular cortex in emotional empathy

The human ability to vicariously share someone else's emotions (i.e., emotional empathy) relies on an extended neural network including regions in the anterior cingulate and insular cortex. Here, we tested the hypothesis that good sleep quality is associated with increased activation in the brain areas underlying emotional empathy. To this aim, we assessed subjective sleep quality in a large sample of healthy young volunteers, and asked participants to complete a computerized emotional empathy task. Then, we asked 16 participants to complete the same task while undergoing functional Magnetic Resonance Imaging (fMRI). After confirming the behavioral relationship between quality of sleep and emotional empathy in the large sample, we conducted a Region of Interest (ROI) analysis on selected ROIs involved in emotional empathy, and measured Blood Oxygen Level Dependent (BOLD) signal change in participants who performed the emotional empathy task in the MRI scanner; additionally, we assessed how the BOLD signal in different brain areas temporally correlated with performance throughout the task (i.e., task‐based functional connectivity). We found increased BOLD signal change in a selective region within the left insula for individuals with better subjective sleep quality. These findings provide the very first evidence that individuals’ sleep quality relates to emotional empathic responses through increased neural activation of a specific area within the insular cortex.     

Processing of subliminal facial expressions of emotion: A behavioral and fMRI study

The recognition of emotional facial expressions is an important means to adjust behavior in social interactions. As facial expressions widely differ in their duration and degree of expressiveness, they often manifest with short and transient expressions below the level of awareness. In this combined behavioral and fMRI study, we aimed at examining whether or not consciously accessible (subliminal) emotional facial expressions influence empathic judgments and which brain activations are related to it. We hypothesized that subliminal facial expressions of emotions masked with neutral expressions of the same faces induce an empathic processing similar to consciously accessible (supraliminal) facial expressions. Our behavioral data in 23 healthy subjects showed that subliminal emotional facial expressions of 40 ms duration affect the judgments of the subsequent neutral facial expressions. In the fMRI study in 12 healthy subjects it was found that both, supra- and subliminal emotional facial expressions shared a widespread network of brain areas including the fusiform gyrus, the temporo-parietal junction, and the inferior, dorsolateral, and medial frontal cortex. Compared with subliminal facial expressions, supraliminal facial expressions led to a greater activation of left occipital and fusiform face areas. We conclude that masked subliminal emotional information is suited to trigger processing in brain areas which have been implicated in empathy and, thereby in social encounters     

Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study

The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal pole, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal pole, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group.