An amygdala response to fearful faces with covered eyes

Findings of amygdala responsiveness to the eye region of fearful faces raise the question of whether eye widening is the only facial cue involved. We used fMRI to investigate the differential amygdala response to fearful versus neutral stimuli for faces, eyes, and for faces in which the eye region was masked. For maximum sensitivity, a block design was used, with a region of interest (ROI) centred on the amygdala which included peri-amygdalar areas. Evidence of amygdala responsiveness to fear compared to neutral stimuli was found for whole faces, eye region only, and for faces with masked eyes. The amygdala can therefore use information from facial regions other than the eyes, allowing it to respond differentially to fearful compared to neutral faces even when the eye region is hidden.     

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.     

Attachment avoidance modulates neural response to masked facial emotion

According to recent models of individual differences in attachment organization, a basic dimension of adult attachment is avoidance. Attachment‐related avoidance corresponds to tendencies to withdraw from close relationships and to an unwillingness to rely on others. In the formation of attachment orientation during infancy facial emotional interaction plays a central role. There exists an inborn very rapid decoding capacity for facial emotional expression. In this study, functional magnetic resonance imaging was used to examine differences in automatic brain reactivity to facial emotions as a function of attachment avoidance in a sample of 51 healthy adults. Pictures of sad and happy faces (which are approach‐related interpersonal signals) were presented masked by neutral faces. The Relationship Scales Questionnaire (RSQ) was used to assess the attachment avoidance. Masked sad faces activated the amygdala, the insula, occipito‐temporal areas, and the somatosensory cortices. Independently from trait anxiety, depressivity, and detection performance, attachment avoidance was found to be inversely related to responses of the primary somatosensory cortex (BA 3) to masked sad faces. A low spontaneous responsivity of the primary somatosensory cortex to negative faces could be a correlate of the habitual unwillingness to deal with partners' distress and needs for proximity. The somatosensory cortices are known to be critically involved in the processes of emotional mimicry and simulation which have the potential to increase social affiliation. Our data are consistent with the idea that people who withdraw from close relationships respond spontaneously to a lesser extent to negative interpersonal emotional signals than securely attached individuals. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Age-related differences in brain regions supporting successful encoding of emotional faces

In an event-related functional Magnetic Resonance Imaging (fMRI) study, younger and older adults were presented with negative emotional (i.e., fearful) and neutral face pictures under incidental learning conditions. They were subsequently given a test of face recognition outside the scanner. Both age groups activated amygdala bilaterally as well as the right hippocampus during successful encoding of the fearful faces. Direct age comparisons revealed greater activation in right amygdala and bilateral hippocampus in the young, whereas older adults showed greater activation in the left insular and right prefrontal cortices. None of these brain areas was activated during successful encoding of neutral faces, suggesting specificity of these brain activation patterns. The results indicate an age-related shift in the neural underpinnings of negative emotional face processing from medial-temporal to neocortical regions.     

A left amygdala mediated network for rapid orienting to masked fearful faces

A rapid response to environmental threat is highly adaptive and fearful facial expressions serve as important threat cues. The biological significance of these threat cues is demonstrated by neuroimaging findings of amygdala responses to backward masked fearful faces. Additionally, behavioral dot-probe studies reveal that backward masked fearful faces modulate spatial attention. However, little is known about the behavioral impact of the amygdala sensitivity to masked fearful faces. Using a dot-probe task with event-related functional magnetic resonance imaging (fMRI), we provide the first evidence that the amygdala is involved in orienting to backward masked fearful faces. Furthermore, this spatial attention-related amygdala response was correlated with activity in the anterior cingulate, superior temporal sulcus, and lingual gyrus.     

Developmental deficits in social perception in autism: the role of the amygdala and fusiform face area

Autism is a severe developmental disorder marked by a triad of deficits, including impairments in reciprocal social interaction, delays in early language and communication, and the presence of restrictive, repetitive and stereotyped behaviors. In this review, it is argued that the search for the neurobiological bases of the autism spectrum disorders should focus on the social deficits, as they alone are specific to autism and they are likely to be most informative with respect to modeling the pathophysiology of the disorder. Many recent studies have documented the difficulties persons with an autism spectrum disorder have accurately perceiving facial identity and facial expressions. This behavioral literature on face perception abnormalities in autism is reviewed and integrated with the functional magnetic resonance imaging (fMRI) literature in this area, and a heuristic model of the pathophysiology of autism is presented. This model posits an early developmental failure in autism involving the amygdala, with a cascading influence on the development of cortical areas that mediate social perception in the visual domain, specifically the fusiform "face area" of the ventral temporal lobe. Moreover, there are now some provocative data to suggest that visual perceptual areas of the ventral temporal pathway are also involved in important ways in representations of the semantic attributes of people, social knowledge and social cognition. Social perception and social cognition are postulated as normally linked during development such that growth in social perceptual skills during childhood provides important scaffolding for social skill development. It is argued that the development of face perception and social cognitive skills are supported by the amygdala-fusiform system, and that deficits in this network are instrumental in causing autism.     

Time-varying amygdala response to emotional faces in generalized social phobia.

BACKGROUND: Individuals with social phobia (SP) have altered behavioral and neural responses to emotional faces and are hypothesized to have deficits in inhibiting emotion-related amygdala responses. We tested for such amygdala deficits to emotional faces in a sample of individuals with SP. METHOD: We used functional magnetic resonance imaging (fMRI) to examine the neural substrates of emotional face processing in 14 generalized SP (gSP) and 14 healthy comparison (HC) participants. Analyses focused on the temporal dynamics of the amygdala, prefrontal cortex (PFC), and fusiform face area (FFA) across blocks of neutral, fear, contempt, anger, and happy faces in gSP versus HC participants. RESULTS: Amygdala responses in participants with gSP occurred later than the HC participants to fear, angry, and happy faces. Parallel PFC responses were found for happy and fear faces. There were no group differences in temporal response patterns in the FFA. CONCLUSIONS: This finding might reflect a neural correlate of atypical orienting responses among individuals with gSP. Commonly reported SP deficits in habituation might reflect neural regions associated with emotional self-evaluations rather than the amygdala. This study highlights the importance of considering time-varying modulation when examining emotion-related processing in individuals with gSP.     

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     

The neural correlates of the dominance dimension of emotion

Emotion has been conceptualized as a dimensional construct, while the number of dimensions – two or three – has been debated. Research has consistently identified two dimensions – valence and arousal – though ample evidence exists that three dimensions are necessary to describe emotion. One proposed third dimension, identified as dominance, is relevant in clinical syndromes, personality and consumer psychology. Dominance refers to an individual's sense of having an ability to affect the environment. Neuroimaging studies have generally focused on the two dimensions of valence and arousal, leaving the neural correlates of dominance unexplored. The current study used functional magnetic resonance imaging to explore the neural basis of dominance in 17 healthy male controls. Participants viewed images from the International Affective Picture System that were selected to represent high and low dominance conditions. Results indicated activation in paralimbic regions, including the bilateral anterior insula for high dominance and the right precuneus for low. The findings of this exploratory study support the consideration of dominance in dimensional models of emotion and suggest that further research is needed to understand the neural representation of dominance in emotional experience.     

Individual differences in social behavior predict amygdala response to fearful facial expressions in Williams syndrome

Williams syndrome (WS) is a genetic condition often paired with abnormal social functioning and behavior. In particular, those with WS are characterized as being relatively hypersocial, overly emotional/empathic, and socially uninhibited or fearless. In addition, WS is associated with abnormal amygdala structure and function. Very little is known however about the relationship between specific social behaviors and altered amygdala function in WS. This study was designed to compare three models that relate abnormal social behavior with amygdala function in WS (indiscriminate sociability, emotional and empathic sociability and social fearlessness). We used a social behavior assessment procedure (Salk Institute Sociability Questionnaire), functional magnetic resonance imaging and an implicit emotion face processing task to test these models. Our findings provide support for a model of abnormal social fearlessness by showing that in WS, abnormal amygdala response to fear is paired with an increased tendency to approach strangers. Specifically, individuals with WS that exhibited less amygdala response to fearful facial expressions (compared to neutral) also exhibited an increased tendency to approach strangers. These findings contribute to our understanding of social and emotional functioning in neurodevelopmental conditions and provide evidence that in WS, amygdala response to fear modulates social behavior.     

Depersonalization disorder: thinking without feeling

Patients with depersonalization disorder (DP) experience a detachment from their own senses and surrounding events, as if they were outside observers. A particularly common symptom is emotional detachment from the surroundings. Using functional magnetic resonance imaging (fMRI), we compared neural responses to emotionally salient stimuli in DP patients, and in psychiatric and healthy control subjects. Six patients with DP, 10 with obsessive–compulsive disorder (OCD), and six volunteers were scanned whilst viewing standardized pictures of aversive and neutral scenes, matched for visual complexity. Pictures were then rated for emotional content. Both control groups rated aversive pictures as much more emotive, and demonstrated in response to these scenes significantly greater activation in regions important for disgust perception, the insula and occipito-temporal cortex, than DP patients (covarying for age, years of education and total extent of brain activation). In DP patients, aversive scenes activated the right ventral prefrontal cortex. The insula was activated only by neutral scenes in this group. Our findings indicate that a core phenomenon of depersonalization — absent subjective experience of emotion — is associated with reduced neural responses in emotion-sensitive regions, and increased responses in regions associated with emotion regulation.     

Integration of cross-modal emotional information in the human brain: an fMRI study

The interaction of information derived from the voice and facial expression of a speaker contributes to the interpretation of the emotional state of the speaker and to the formation of inferences about information that may have been merely implied in the verbal communication. Therefore, we investigated the brain processes responsible for the integration of emotional information originating from different sources. Although several studies have reported possible sites for integration, further investigation using a neutral emotional condition is required to locate emotion-specific networks. Using functional magnetic resonance imaging (fMRI), we explored the brain regions involved in the integration of emotional information from different modalities in comparison to those involved in integrating emotionally neutral information. There was significant activation in the superior temporal gyrus (STG); inferior frontal gyrus (IFG); and parahippocampal gyrus, including the amygdala, under the bimodal versus the unimodal condition, irrespective of the emotional content. We confirmed the results of previous studies by finding that the bimodal emotional condition elicited strong activation in the left middle temporal gyrus (MTG), and we extended this finding to locate the effects of emotional factors by using a neutral condition in the experimental design. We found anger-specific activation in the posterior cingulate, fusiform gyrus, and cerebellum, whereas we found happiness-specific activation in the MTG, parahippocampal gyrus, hippocampus, claustrum, inferior parietal lobule, cuneus, middle frontal gyrus (MFG), IFG, and anterior cingulate. These emotion-specific activations suggest that each emotion uses a separate network to integrate bimodal information and shares a common network for cross-modal integration.     

Age-related differences in response regulation as revealed by functional MRI

This fMRI study studied age-related differences in neural activities during response regulation. Twenty-one male participants from two age groups, a younger group and an older group (mean ages: 29.9 and 65.2 years, respectively), were scanned while performing a task with response compatibility manipulation. They were presented with a sequence of arrowheads that pointed either upward or downward. In the "Response Compatible" condition, they were required to press an up or a down button consistent with the direction of the arrowhead. In the "Response Incompatible" condition, they were required to press the button opposite to the arrowhead direction so that an upward arrow should elicit a down response, and vice versa. Findings showed age-related differences in response regulation in several brain regions, including the right frontal, the right cingulate, and the left inferior parietal cortexes. The findings suggested a higher level of neural activity in the right prefrontal and left inferior parietal regions during response regulation for the older adults than for the younger adults.     

Sex-related differences in neural activity during emotion regulation

The sex disparity in the development of depression has long been an important research topic, but the sex-related differences in neural activity during emotion regulation have been less thoroughly studied. It was hypothesized that, during the regulation of emotion, there would be more activation in the prefrontal regions implicated in cognitive processing for males, while there would be more activation in the prefrontal regions implicated in affective processing for females. This fMRI study recruited 12 females and 12 males who were required to view or to regulate the negative and positive emotion induced by some emotion-arousing pictures. During the regulation of negative emotion, both males and females had stronger activation in the left anterior cingulate gyrus, but males showed more activation in the prefrontal regions in general, including the left dorsolateral and lateral orbitofrontal gyrus as well as the right anterior cingulate gyrus, while females only showed stronger activation in the left medial orbitofrontal gyrus. For the regulation of positive emotion, both males and females showed stronger activation in the left dorsomedial prefrontal gyrus, but males were found to also have stronger activity in the left lateral orbitofrontal gyrus. It was concluded that there are common as well as sex-specific sets of brain regions involved in regulating negative and positive emotion, and the findings may have significant implications for females’ vulnerability to developing depression.     

Differential neural activity and connectivity for processing one's own face: A preliminary report

The experience of self is unique and pivotal to clinically relevant cognitive and emotional functions. However, well-controlled data on specialized brain regions and functional networks underlying the experience of self remain limited. This functional magnetic resonance imaging study investigated neural activity and connectivity specific to processing one's own face in healthy women by examining neural responses to the pictures of the subjects' own faces in contrast to faces of their own mothers, female friends and strangers during passive viewing, emotional and self-relevance evaluations. The processing of one's own face in comparison to processing of familiar faces revealed significant activity in right anterior insula (AI) and left inferior parietal lobule (IPL), and less activity in right posterior cingulate/precuneus (PCC/PCu) across all tasks. Further, the seed-based correlation analysis of right AI, and left IPL, showed differential functional networks in self and familiar faces contrasts. There were no differences in valence and saliency ratings between self and familiar others. Our preliminary results suggest that the self-experience cued by self-face is processed predominantly by brain regions and related networks that link interoceptive feelings and sense of body ownership to self-awareness and less by regions of higher order functioning such as autobiographical memories.     

Brain activation predicts treatment improvement in patients with major depressive disorder

Major depressive disorder (MDD) is associated with alterations in brain function that might be useful for therapy evaluation. The current study aimed to identify predictors for therapy improvement and to track functional brain changes during therapy. Twenty-one drug-free patients with MDD underwent functional MRI twice during performance of an emotional perception task: once before and once after 4 weeks of antidepressant treatment (mirtazapine or venlafaxine). Twelve healthy controls were investigated once with the same methods. A significant difference between groups was a relative greater activation of the right dorsolateral prefrontal cortex (dlPFC) in the patients vs. controls. Before treatment, patients responding better to pharmacological treatment showed greater activation in the dorsomedial PFC (dmPFC), posterior cingulate cortex (pCC) and superior frontal gyrus (SFG) when viewing of negative emotional pictures was compared with the resting condition. Activations in the caudate nucleus and insula contrasted for emotional compared to neutral stimuli were also associated with successful treatment. Responders had also significantly higher levels of activation, compared to non-responders, in a range of other brain regions. Brain activation related to treatment success might be related to altered self-referential processes and a differential response to external emotional stimuli, suggesting differences in the processing of emotionally salient stimuli between those who are likely to respond to pharmacological treatment and those who will not. The present investigation suggests the pCC, dmPFC, SFG, caudate nucleus and insula may have a key role as a biological marker for treatment response and predictor for therapeutic success.     

Short Term Exposure to a Violent Video Game Induces Changes in Frontolimbic Circuitry in Adolescents

Despite evidence of effects of violent video game play on behavior, the underlying neuronal mechanisms involved in these effects remain poorly understood. We report a functional MRI (fMRI) study during two modified Stroop tasks performed immediately after playing a violent or nonviolent video game. Compared with the violent video game group, the nonviolent video game group demonstrated more activation in some regions of the prefrontal cortex during the Counting Stroop task. In contrast to the violent video game group, significantly stronger functional connectivity between left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) was identified in the nonviolent video game group. During an Emotional Stroop task, the violent video game group showed more activity in the right amygdala and less activation in regions of the medial prefrontal cortex (MPFC). Furthermore, functional connectivity analysis revealed the negative coupling between right amygdala and MPFC in the nonviolent video game group. By contrast, no significant functional connectivity between right amygdala and MPFC was found in the violent video game group. These results suggest differential engagement of neural circuitry in response to short term exposure to a violent video game as compared to a nonviolent video game.     

Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder

Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRIs), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of amygdala activation by negative facial expressions in MDD patients. We treated fifteen MDD patients (22–55 years) with paroxetine 20–50 mg/day. After 6 and 12 weeks, we quantified (1) clinical response (≥50% decrease in Hamilton Depression Rating Scale (HDRS), (2) SERT occupancy in both amygdala measured by repeated [¹²³I]β-CIT single photon emission computed tomography (SPECT), and (3) amygdala activation when viewing fearful and angry (negative) faces with repeated functional MRI scans. Response rates were 4/15 and 9/15 at 6 and 12 weeks, respectively. Attenuation of left amygdala activation was associated with amygdala SERT occupancy (P=0.006) and response (P=0.015). This association may provide a rationale for decreased limbic activity seen during treatment of MDD. It might also explain the rapid decrease in negative attentional bias and amygdala activation caused by SSRIs.     

MRI lesions masked by brain development: a case of infant-onset focal epilepsy

A 3-month-old male presented with right-side–dominant focal seizures. Focal spikes were observed on the left side of an electroencephalogram obtained at the time of onset. The immature development in the left middle temporal lobe was observed by initial magnetic resonance imaging (MRI). The hypoperfusion in the left temporal lobe observed with single-photon computed tomography was consistent with MRI findings. These MRI findings were not observed in a second MRI at 11 months of age. This observation may explain one of the causes of infant-onset focal epilepsy.