The serotonin transporter gene polymorphism and the effect of baseline on amygdala response to emotional faces

Previous research has found that a common polymorphism in the serotonin transporter gene (5-HTTLPR) is an important mediator of individual differences in brain responses associated with emotional behaviour. In particular, relative to individuals homozygous for the l-allele, carriers of the s-allele display heightened amygdala activation to emotional compared to non-emotional stimuli. However, there is some debate as to whether this difference is driven by increased activation to emotional stimuli, resting baseline differences between the groups, or decreased activation to neutral stimuli. We performed functional imaging during an implicit facial expression processing task in which participants viewed angry, sad and neutral faces. In addition to neutral faces, we included two further baseline conditions, houses and fixation. We found increased amygdala activation in s-allele carriers relative to l-homozygotes in response to angry faces compared to neutral faces, houses and fixation. When comparing neutral faces to houses or fixation, we found no significant difference in amygdala response between the two groups. In addition, there was no significant difference between the groups in response to fixation when compared with a houses baseline. Overall, these results suggest that the increased amygdala response observed in s-allele carriers to emotional faces is primarily driven by an increased response to emotional faces rather than a decreased response to neutral faces or an increased resting baseline. The results are discussed in relation to the tonic and phasic hypotheses of 5-HTTLPR-mediated modulation of amygdala activity.     

Influence of Emotional Processing on Working Memory in Schizophrenia

Research on emotional processing in schizophrenia suggests relatively intact subjective responses to affective stimuli “in the moment.” However, neuroimaging evidence suggests diminished activation in brain regions associated with emotional processing in schizophrenia. We asked whether given a more vulnerable cognitive system in schizophrenia, individuals with this disorder would show increased or decreased modulation of working memory (WM) as a function of the emotional content of stimuli compared with healthy control subjects. In addition, we examined whether higher anhedonia levels were associated with a diminished impact of emotion on behavioral and brain activation responses. In the present study, 38 individuals with schizophrenia and 32 healthy individuals completed blocks of a 2-back WM task in a functional magnetic resonance imaging scanning session. Blocks contained faces displaying either only neutral stimuli or neutral and emotional stimuli (happy or fearful faces), randomly intermixed and occurring both as targets and non-targets. Both groups showed higher accuracy but slower reaction time for negative compared to neutral stimuli. Individuals with schizophrenia showed intact amygdala activity in response to emotionally evocative stimuli, but demonstrated altered dorsolateral prefrontal cortex (DLPFC) and hippocampal activity while performing an emotionally loaded WM-task. Higher levels of social anhedonia were associated with diminished amygdala responses to emotional stimuli and increased DLPFC activity in individuals with schizophrenia. Emotional arousal may challenge dorsal-frontal control systems, which may have both beneficial and detrimental influences. Our findings suggest that disturbances in emotional processing in schizophrenia relate to alterations in emotion-cognition interactions rather than to the perception and subjective experience of emotion per se.     

Amygdala response to both positively and negatively valenced stimuli

Human lesion and functional imaging data suggest a central role for the amygdala in the processing of negative stimuli. To determine whether the amygdala's role in affective processing extends beyond negative stimuli, subjects viewed pictures that varied in emotional content (positive vs negative valence) and arousal level (high vs low) while undergoing functional magnetic resonance imaging. Amygdala activation, relative to a low arousal and neutral valence picture baseline, was significantly increased for both positively and negatively valenced stimuli and did not differ for the two valences. There were no laterality effects. Whereas arousal level appeared to modulate the amygdala response for negative stimuli, all positively valenced pictures (both high and low in arousal) produced significant amygdala responses. These results clearly demonstrate a role for the amygdala in processing emotional stimuli that extends beyond negative and fearful stimuli.     

Neural correlates of positive and negative emotion regulation

The ability to cope adaptively with emotional events by volitionally altering one's emotional reactions is important for psychological and physical health as well as social interaction. Cognitive regulation of emotional responses to aversive events engages prefrontal regions that modulate activity in emotion-processing regions such as the amygdala. However, the neural correlates of the regulation of positive emotions remain largely unexplored. We used event-related functional magnetic resonance imaging to examine the neural correlates of cognitively increasing and decreasing emotional reactions to positive and negative stimuli. Participants viewed negative, positive, and neutral pictures while attempting to increase, decrease, or not alter their emotional reactions. Subjective reactions were assessed via on-line ratings. Consistent with previous studies, increasing negative and positive emotion engaged primarily left-lateralized prefrontal regions, whereas decreasing emotion activated bilateral prefrontal regions. Different activations unique to increasing versus decreasing emotion were observed for positive and negative stimuli: Unique increase-related activations were observed only for positive stimuli, whereas unique decrease-related activations were observed only for negative stimuli. Regulation also modulated activity in the amygdala, a key emotion-processing region. Regulation effects on amygdala activity were larger for positive than for negative stimuli, potentially reflecting a greater malleability of positive emotional reactions. Increasing and decreasing positive and negative emotion can thus increase and decrease subjective reactions and associated amygdala activity in line with regulatory goals, and is associated with different patterns of prefrontal activation as a function of emotional valence and regulatory goal.     

Mindfulness and emotion regulation—an fMRI study

Mindfulness—an attentive non-judgmental focus on present experiences—is increasingly incorporated in psychotherapeutic treatments as a skill fostering emotion regulation. Neurobiological mechanisms of actively induced emotion regulation are associated with prefrontally mediated down-regulation of, for instance, the amygdala. We were interested in neurobiological correlates of a short mindfulness instruction during emotional arousal. Using functional magnetic resonance imaging, we investigated effects of a short mindfulness intervention during the cued expectation and perception of negative and potentially negative pictures (50% probability) in 24 healthy individuals compared to 22 controls. The mindfulness intervention was associated with increased activations in prefrontal regions during the expectation of negative and potentially negative pictures compared to controls. During the perception of negative stimuli, reduced activation was identified in regions involved in emotion processing (amygdala, parahippocampal gyrus). Prefrontal and right insular activations when expecting negative pictures correlated negatively with trait mindfulness, suggesting that more mindful individuals required less regulatory resources to attenuate emotional arousal. Our findings suggest emotion regulatory effects of a short mindfulness intervention on a neurobiological level.     

The effects of catechol O-methyltransferase genotype on brain activation elicited by affective stimuli and cognitive tasks

Catechol-O-methyltransferase (COMT) degrades the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A functional polymorphism in the COMT gene (val158 met) accounts for a four-fold variation in enzyme activity. The low activity met158 allele has been associated with improved working memory, executive functioning, and attentional control, but also with a higher risk of anxiety-related behaviors. In spite of the strong effect of the COMT genotype on enzyme activity, its effects on behavior are moderate, accounting for only 4% of variance in task performance. Studies of individuals with intermediate phenotypes during activities such as task-dependent brain activation, may more sensitively detect gene effects on the brain. A series of studies using functional magnetic resonance imaging (fMRI) assessed the effects of the COMT val158 met genotype on central processing during working memory, attentional control, and emotional tasks. fMRI revealed a more focused response in the prefrontal cortex (PFC) of met158 allele carriers during a working memory task. A comparable effect during the performance of an attentional control task in the cingulate cortex was also observed. These data indicate that met158 allele load is associated with improved processing efficiency in the PFC and cingulate, which might be due to lower prefrontal dopamine (DA) metabolism, higher DA concentrations, and an increased neuronal signal-to-noise ratio during information processing. During performance of an emotional task, reactivity to unpleasant visual stimuli was positively correlated with the number of met158 alleles in the amygdala, as well as in other limbic and paralimbic nodes. This increased limbic reactivity to unpleasant stimuli might be the underlying cause of the lower emotional resilience against negative mood states observed in individuals with a higher met158 allele load. Thus the met158 allele seems to be beneficial during the performance of working memory and attention-related tasks, whereas the val158 allele appears to be advantageous during the processing of aversive emotional stimuli.     

History of childhood maltreatment augments dorsolateral prefrontal processing of emotional valence in PTSD

Posttraumatic stress disorder (PTSD) is characterized by conflicting findings of both increased and decreased amygdala and prefrontal reactivity to threat or trauma stimuli. Childhood maltreatment (CM), a potent risk factor for PTSD, exerts long-lasting influences on threat processing and prefrontal-amygdala function. This suggests that CM history may influence PTSD neural phenotypes related to threat processing. Here, we adapt a well-characterized emotional conflict paradigm to investigate CM effects on both emotional conflict and emotional valence processing within PTSD stratified by task relevance. Forty-two individuals with PTSD (22 reporting extensive CM history (PTSD-CM)) and 20 trauma-exposed healthy controls (TEHCs) underwent functional magnetic resonance imaging while identifying affect of emotional faces (fear and happy) overlaid with a goal-irrelevant emotional distractor word (“FEAR” or “HAPPY”). We examined effects of CM on conflict, conflict adaptation, valence-related activation (fear vs. happy) for goal-relevant (face) and goal-irrelevant stimuli (word), and valence effects in interaction with goal-relevancy (face vs. word). Though no activation differences between groups were observed for conflict contrasts nor for valence effects in the amygdala, CM status interacted with valence processing differences as a function of goal relevance in the left dorsolateral prefrontal cortex (dlPFC). Here, PTSD-CM displayed greater activation relative to PTSD to negative valence when stimuli were goal-irrelevant. CM history also moderated relationships between activation abnormalities and PTSD re-experiencing symptoms. These findings provide initial evidence that CM history augments dorsolateral prefrontal bias to implicitly processed stimulus valence in PTSD.     

Neural correlates of processing emotional prosody in unipolar depression

Major depressive disorder (MDD) is characterized by a biased emotion perception. In the auditory domain, MDD patients have been shown to exhibit attenuated processing of positive emotions expressed by speech melody (prosody). So far, no neuroimaging studies examining the neural basis of altered processing of emotional prosody in MDD are available. In this study, we addressed this issue by examining the emotion bias in MDD during evaluation of happy, neutral, and angry prosodic stimuli on a five‐point Likert scale during functional magnetic resonance imaging (fMRI). As expected, MDD patients rated happy prosody less intense than healthy controls (HC). At neural level, stronger activation in the middle superior temporal gyrus (STG) and the amygdala was found in all participants when processing emotional as compared to neutral prosody. MDD patients exhibited an increased activation of the amygdala during processing prosody irrespective of valence while no significant differences between groups were found for the STG, indicating that altered processing of prosodic emotions in MDD occurs rather within the amygdala than in auditory areas. Concurring with the valence‐specific behavioral effect of attenuated evaluation of positive prosodic stimuli, activation within the left amygdala of MDD patients correlated with ratings of happy, but not neutral or angry prosody. Our study provides first insights in the neural basis of reduced experience of positive information and an abnormally increased amygdala activity during prosody processing.     

Increased amygdala activation to neutral faces is associated with better face memory performance

Recent evidence suggests that the role of the amygdala may extend beyond threat detection to include processing socially relevant stimuli in general. Thus, we investigated perception and memory for neutral faces; a stimulus-type that lacks emotional valence yet contains relevant social information. Participants viewed neutral faces or houses when undergoing functional MRI. Neutral face memory testing was conducted outside the scanner. In the functional MRI of faces vs. houses contrast, significant bilateral activation in the amygdala and lateral fusiform gyrus was observed. Increased bilateral amygdala activation was associated with better delayed-memory performance. These findings indicate that the role of the amygdala may include processing neutral yet socially relevant stimuli. Further, amygdala activation, independent of emotional valence, appears to be associated with memory enhancement.     

Sex differences in brain activation to emotional stimuli: a meta-analysis of neuroimaging studies

Substantial sex differences in emotional responses and perception have been reported in previous psychological and psychophysiological studies. For example, women have been found to respond more strongly to negative emotional stimuli, a sex difference that has been linked to an increased risk of depression and anxiety disorders. The extent to which such sex differences are reflected in corresponding differences in regional brain activation remains a largely unresolved issue, however, in part because relatively few neuroimaging studies have addressed this issue. Here, by conducting a quantitative meta-analysis of neuroimaging studies, we were able to substantially increase statistical power to detect sex differences relative to prior studies, by combining emotion studies which explicitly examined sex differences with the much larger number of studies that examined only women or men. We used an activation likelihood estimation approach to characterize sex differences in the likelihood of regional brain activation elicited by emotional stimuli relative to non-emotional stimuli. We examined sex differences separately for negative and positive emotions, in addition to examining all emotions combined. Sex differences varied markedly between negative and positive emotion studies. The majority of sex differences favoring women were observed for negative emotion, whereas the majority of the sex differences favoring men were observed for positive emotion. This valence-specificity was particularly evident for the amygdala. For negative emotion, women exhibited greater activation than men in the left amygdala, as well as in other regions including the left thalamus, hypothalamus, mammillary bodies, left caudate, and medial prefrontal cortex. In contrast, for positive emotion, men exhibited greater activation than women in the left amygdala, as well as greater activation in other regions including the bilateral inferior frontal gyrus and right fusiform gyrus. These meta-analysis findings indicate that the amygdala, a key region for emotion processing, exhibits valence-dependent sex differences in activation to emotional stimuli. The greater left amygdala response to negative emotion for women accords with previous reports that women respond more strongly to negative emotional stimuli, as well as with hypothesized links between increased neurobiological reactivity to negative emotion and increased prevalence of depression and anxiety disorders in women. The finding of greater left amygdala activation for positive emotional stimuli in men suggests that greater amygdala responses reported previously for men for specific types of positive stimuli may also extend to positive stimuli more generally. In summary, this study extends efforts to characterize sex differences in brain activation during emotion processing by providing the largest and most comprehensive quantitative meta-analysis to date, and for the first time examining sex differences as a function of positive vs. negative emotional valence. The current findings highlight the importance of considering sex as a potential factor modulating emotional processing and its underlying neural mechanisms, and more broadly, the need to consider individual differences in understanding the neurobiology of emotion.     

Cognitive appraisal and life stress moderate the effects of the 5-HTTLPR polymorphism on amygdala reactivity

The short allele of the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism is associated with increased amygdala activation in response to emotional stimuli. Although top-down processes may moderate this association, available evidence is conflicting, showing the genotype influence on amygdala reactivity to be either decreased or increased during emotion regulation. Because the effects of the 5-HTTLPR polymorphism on amygdala reactivity are also conditional on self-reported life stress, differences in life stress exposure may account for this apparent discrepancy. Here, we hypothesized that self-reported life stress would moderate the relationships between genotype, cognitive appraisal, and amygdala reactivity. Forty-five healthy never-depressed subjects were presented with emotional stimuli and performed two cognitive tasks: a self-referential task and an emotion-labeling task. Life-stress exposure was measured through a semistructured interview. First, there was a genotype × condition interaction in the right amygdala: short allele carriers displayed increased amygdala activation and decreased functional connectivity with the subgenual anterior cingulate cortex in self-referential processing versus emotion labeling. Second, in line with our hypothesis, there was a genotype × condition × stress interaction in bilateral amygdala the amygdala activation during self-referential processing was negatively correlated with self-reported life stress in short allele carriers and positively in individuals homozygous for the long allele, whereas an opposite pattern was observed during emotion labeling. These results confirm that the influence of the 5-HTTLPR polymorphism on amygdala reactivity is at least partially under cognitive control. Additionally, they suggest that measuring life stress exposure is a critical step when imaging genetics.     

Emotional self-reference: brain structures involved in the processing of words describing one's own emotions

The present functional magnetic resonance imaging study investigated the role of emotion-related (e.g., amygdala) and self-related brain structures (MPFC in particular) in the processing of emotional words varying in stimulus reference. Healthy subjects (N = 22) were presented with emotional (pleasant or unpleasant) or neutral words in three different conditions: (1) self (e.g., my fear), (2) other (e.g., his fear) and (3) no reference (e.g., the fear). Processing of unpleasant words was associated with increased amygdala and also insula activation across all conditions. Pleasant stimuli were specifically associated with increased activation of amygdala and insula when related to the self (vs. other and no reference). Activity in the MPFC (vMPFC in particular) and anterior cingulate cortex (ACC) was preferentially increased during processing of self-related emotional words (vs. other and no reference). These results demonstrate that amygdala activation in response to emotional stimuli is modulated by stimulus reference and that brain structures implicated in emotional and self-related processing might be important for the subjective experience of one's own emotions.     

Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals.

BACKGROUND: Previous research suggests that depressed individuals engage in prolonged elaborative processing of emotional information. A computational neural network model of emotional information processing suggests this process involves sustained amygdala activity in response to processing negative features of information. This study examined whether brain activity in response to emotional stimuli was sustained in depressed individuals, even following subsequent distracting stimuli. METHODS: Seven depressed and 10 never-depressed individuals were studied using event-related functional magnetic resonance imaging during alternating 15-sec emotional processing (valence identification) and non-emotional processing (Sternberg memory) trials. Amygdala regions were traced on high-resolution structural scans and co-registered to the functional data. The time course of activity in these areas during emotional and non-emotional processing trials was examined. RESULTS: During emotional processing trials, never-depressed individuals displayed amygdalar responses to all stimuli, which decayed within 10 sec. In contrast, depressed individuals displayed sustained amygdala responses to negative words that lasted throughout the following non-emotional processing trials (25 sec later). The difference in sustained amygdala activity to negative and positive words was moderately related to self-reported rumination. CONCLUSIONS: Results suggest that depression is associated with sustained activity in brain areas responsible for coding emotional features.     

Negative content enhances stimulus‐specific cerebral activity during free viewing of pictures,faces, and words

Negative visual stimuli have been found to elicit stronger brain activation than do neutral stimuli. Such emotion effects have been shown for pictures, faces, and words alike, but the literature suggests stimulus‐specific differences regarding locus and lateralization of the activity. In the current functional magnetic resonance imaging study, we directly compared brain responses to passively viewed negative and neutral pictures of complex scenes, faces, and words (nouns) in 43 healthy participants (21 males) varying in age and demographic background. Both negative pictures and faces activated the extrastriate visual cortices of both hemispheres more strongly than neutral ones, but effects were larger and extended more dorsally for pictures, whereas negative faces additionally activated the superior temporal sulci. Negative words differentially activated typical higher‐level language processing areas such as the left inferior frontal and angular gyrus. There were small emotion effects in the amygdala for faces and words, which were both lateralized to the left hemisphere. Although pictures elicited overall the strongest amygdala activity, amygdala response to negative pictures was not significantly stronger than to neutral ones. Across stimulus types, emotion effects converged in the left anterior insula. No gender effects were apparent, but age had a small, stimulus‐specific impact on emotion processing. Our study specifies similarities and differences in effects of negative emotional content on the processing of different types of stimuli, indicating that brain response to negative stimuli is specifically enhanced in areas involved in processing of the respective stimulus type in general and converges across stimuli in the left anterior insula.     

Individual differences in amygdala and ventromedial prefrontal cortex activity are associated with evaluation speed and psychological well-being

Using functional magnetic resonance imaging, we examined whether individual differences in amygdala activation in response to negative relative to neutral information are related to differences in the speed with which such information is evaluated, the extent to which such differences are associated with medial prefrontal cortex function, and their relationship with measures of trait anxiety and psychological well-being (PWB). Results indicated that faster judgments of negative relative to neutral information were associated with increased left and right amygdala activation. In the prefrontal cortex, faster judgment time was associated with relative decreased activation in a cluster in the ventral anterior cingulate cortex (ACC, BA 24). Furthermore, people who were slower to evaluate negative versus neutral information reported higher PWB. Importantly, higher PWB was strongly associated with increased activation in the ventral ACC for negative relative to neutral information. Individual differences in trait anxiety did not predict variation in judgment time or in amygdala or ventral ACC activity. These findings suggest that people high in PWB effectively recruit the ventral ACC when confronted with potentially aversive stimuli, manifest reduced activity in subcortical regions such as the amygdala, and appraise such information as less salient as reflected in slower evaluative speed.     

Neural correlates of alexithymia: A meta-analysis of emotion processing studies

Alexithymia is a personality trait characterized by difficulties in the experience and cognitive processing of emotions. It is considered a risk factor for a range of psychiatric and neurological disorders. Functional neuroimaging studies investigating the neural correlates of alexithymia have reported inconsistent results. To integrate previous findings, we conducted a parametric coordinate-based meta-analysis including fifteen neuroimaging studies on emotion processing in alexithymia. During the processing of negative emotional stimuli, alexithymia was associated with a diminished response of the amygdala, suggesting decreased attention to such stimuli. Negative stimuli additionally elicited decreased activation in supplementary motor and premotor brain areas and in the dorsomedial prefrontal cortex, possibly underlying poor empathic abilities and difficulties in emotion regulation associated with alexithymia. Positive stimuli elicited decreased activation in the right insula and precuneus, suggesting reduced emotional awareness in alexithymia regarding positive affect. Independent of valence, higher (presumably compensatory) activation was found in the dorsal anterior cingulate possibly indicating increased cognitive demand. These results suggest valence-specific as well as valence-independent effects of alexithymia on the neural processing of emotions.     

Increased amygdala and insula activation during emotion processing in anxiety-prone subjects

OBJECTIVE: Increased amygdala reactivity during processing of certain types of emotional stimuli (e.g., fear, anger) has been observed in patients with anxiety disorders such as social phobia and posttraumatic stress disorder (PTSD). It is uncertain whether this heightened amygdala reactivity is specific to treatment-seeking patients with anxiety disorders or is a general feature of individuals with increased anxiety-related temperamental traits. METHOD: Thirty-two physically healthy subjects 18-21 years old were recruited from a large pool of college students. Of these, 16 were chosen on the basis of scoring in the upper-15th percentile on a measure of trait anxiety (anxiety-prone group), and 16 were chosen on the basis of scoring in the normative range (40th-60th percentile). Subjects participated in functional magnetic resonance imaging (fMRI) during an emotion face assessment task that has been shown to reliably engage amygdala and associated limbic structures. RESULTS: Anxiety-prone subjects had significantly greater bilateral amygdala and insula activation to emotional faces than did the anxiety-normative comparison subjects. Higher scores on several measures assessing anxiety proneness (e.g., neuroticism, trait anxiety, and anxiety sensitivity) were associated with greater activation of the amygdala (predominantly left-sided) and the anterior insula (bilateral). CONCLUSIONS: Increased amygdala and insula reactivity to certain types of emotional processing is seen in young adults with increased anxiety-related temperamental traits. Therefore, this brain emotion-processing profile may be a functional endophenotype for proneness to (certain kinds of) anxiety disorders.     

FMRI activations of amygdala, cingulate cortex, and auditory cortex by infant laughing and crying

One of the functions of emotional vocalizations is the regulation of social relationships like those between adults and children. Listening to infant vocalizations is known to engage amygdala as well as anterior and posterior cingulate cortices. But, the functional relationships between these structures still need further clarification. Here, nonparental women and men listened to laughing and crying of preverbal infants and to vocalization-derived control stimuli, while performing a pure tone detection task during low-noise functional magnetic resonance imaging. Infant vocalizations elicited stronger activation in amygdala and anterior cingulate cortex (ACC) of women, whereas the alienated control stimuli elicited stronger activation in men. Independent of listeners' gender, auditory cortex (AC) and posterior cingulate cortex (PCC) were more strongly activated by the control stimuli than by infant laughing or crying. The gender-dependent correlates of neural activity in amygdala and ACC may reflect neural predispositions in women for responses to preverbal infant vocalizations, whereas the gender-independent similarity of activation patterns in PCC and AC may reflect more sensory-based and cognitive levels of neural processing. In comparison to our previous work on adult laughing and crying, the infant vocalizations elicited manifold higher amygdala activation.     

Mesolimbic interaction of emotional valence and reward improves memory formation

Animal studies suggest that dopaminergic neuromodulation is critical for hippocampal memory formation. Compatible with this notion, recent functional imaging evidence in humans showed that reward modulates the hippocampus-dependent formation of episodic memories through activation of areas belonging to the mesolimbic dopaminergic system, including the ventral striatum and substantia nigra/ventral tegmental area (SN/VTA). However, the amygdala is also closely embedded within this mesolimbic circuitry with reciprocal connections to the SN/VTA, raising the possibility that emotionally valenced stimuli might also interact with hippocampal encoding through dopaminergic neuromodulation. By the same token, emotional processing in the amygdala might be affected by reward-related processing in the mesolimbic system. In an event-related functional magnetic resonance imaging study, reward-related activity in the ventral striatum was enhanced by the concurrent presentation of emotionally positive but not emotionally negative stimuli. Emotional processing in the amygdala, on the other hand, was not affected by reward. One day after study, recollection of the positive stimuli was better when they were associated with reward at encoding as compared with unrewarded positive stimuli. The findings are compatible with the notion that the output of the reward system and memory formation in the hippocampus is influenced by positive emotional valence and suggest that the ventral striatum is a key structure for this modulation.     

Common and distinct brain activation to threat and safety signals in social phobia

BACKGROUND: Little is known about the functional neuroanatomy underlying the processing of emotional stimuli in social phobia. OBJECTIVES: To investigate specific brain activation that is associated with the processing of threat and safety signals in social phobics. METHODS: Using functional magnetic resonance imaging, brain activation was measured in social phobic and nonphobic subjects during the presentation of angry, happy and neutral facial expressions under free viewing conditions. RESULTS: Compared to controls, phobics showed increased activation of extrastriate visual cortex regardless of facial expression. Angry, but not neutral or happy, faces elicited greater insula responses in phobics. In contrast, both angry and happy faces led to increased amygdala activation in phobics. CONCLUSIONS: The results support the hypothesis that the amygdala is involved in the processing of negative and positive stimuli. Furthermore, social phobics respond sensitively not only to threatening but also to accepting faces and common and distinct neural mechanisms appear to be associated with the processing of threat versus safety signals.