Fear is fast in phobic individuals: amygdala activation in response to fear-relevant stimuli.

BACKGROUND: Two core characteristics of pathologic fear are its rapid onset and resistance to cognitive regulation. We hypothesized that activation of the amygdala early in the presentation of fear-relevant visual stimuli would distinguish phobics from nonphobics. METHODS: Chronometry of amygdala activation to phobia-relevant pictures was assessed in 13 spider phobics and 14 nonphobics using functional magnetic resonance imaging (fMRI). RESULTS: Blood oxygen level-dependent (BOLD) responses in the amygdala early in picture processing consistently differentiated between phobic and nonphobic subjects, as well as between phobogenic and nonphobogenic stimuli among phobics. Furthermore, amygdalar BOLD responses associated with timing but not magnitude of activation predicted affective responses to phobogenic stimuli. Computational modeling procedures were used to identify patterns of neural activation in the amygdala that could yield the observed BOLD data. These data suggest that phobic responses were characterized by strong but brief amygdala responses, whereas nonphobic responses were weaker and more sustained. CONCLUSIONS: Results are discussed in the context of the amygdala's role in rapid threat detection and the vigilance-avoidance hypothesis of anxiety. These data highlight the importance of examining the neural substrates of the immediate impact of phobogenic stimuli for understanding pathological fear.     

Motherhood and theory of mind: increased activation in the posterior cingulate cortex and insulae

Despite growing evidence on effects of parenthood on social understanding, little is known about the influence of parenthood on theory of mind (ToM), the capacity to infer mental and affective states of others. It is also unclear whether any possible effects of parenthood on ToM would generalise to inferring states of adults or are specific to children. We investigated neural activation in mothers and women without children while they predicted action intentions from child and adult faces. Region-of-interest analyses showed stronger activation in mothers in the bilateral posterior cingulate cortex, precuneus (ToM-related areas) and insulae (emotion-related areas). Whole-brain analyses revealed that mothers compared to non-mothers more strongly activated areas including the left angular gyrus and the ventral prefrontal cortex but less strongly activated the right supramarginal gyrus and the dorsal prefrontal cortex. These differences were not specific to child stimuli but occurred in response to both adult and child stimuli and might indicate that mothers and non-mothers employ different strategies to infer action intentions from affective faces. Whether these general differences in affective ToM between mothers and non-mothers are due to biological or experience-related changes should be subject of further investigation.     

Social status modulates the neural response to unfairness

In human society, which is organized by social hierarchies, resources are usually allocated unequally and based on social status. In this study, we analyze how being endowed with different social statuses in a math competition affects the perception of fairness during asset allocation in a subsequent Ultimatum Game (UG). Behavioral data showed that when participants were in high status, they were more likely to reject unfair UG offers than in low status. This effect of social status correlated with activity in the right anterior insula (rAI) and with the functional connectivity between the rAI and a region in the anterior middle cingulate cortex, indicating that these two brain regions are crucial for integrating contextual factors and social norms during fairness perception. Additionally, there was an interaction between social status and UG offer fairness in the amygdala and thalamus, implicating the role of these regions in the modulation of social status on fairness perception. These results demonstrate the effect of social status on fairness perception and the potential neural underpinnings for this effect.     

Sustained activation of the hippocampus in response to fearful faces in schizophrenia.

BACKGROUND: In healthy individuals, the activity of the medial temporal lobe habituates rapidly with the repeated presentation of a stimulus. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that habituation of the medial temporal lobe is reduced in schizophrenia. METHODS: During fMRI scanning, fearful and happy faces were presented repeatedly to healthy control subjects (n =16) and patients with schizophrenia (n =18). Habituation of medial temporal lobe structures was measured by comparing the hemodynamic response occurring during the early and late portions of the presentation of each face. RESULTS: Control subjects demonstrated significant medial temporal lobe habituation to fearful but not to happy faces. In contrast, patients with schizophrenia did not demonstrate medial temporal lobe habituation in response to fearful or happy faces. In a direct, between-group comparison, right hippocampal habituation to fearful faces was significantly greater in control subjects than in the schizophrenia patients. Also, there were no significant differences between the patients and control subjects in the early medial temporal lobe response to fearful faces, suggesting that attenuated hippocampal habituation in schizophrenia is not associated with a reduction in initial activation. CONCLUSIONS: These findings suggest that there is abnormal modulation of hippocampal responses to fearful faces in schizophrenia.     

Attention and amygdala activity: an fMRI study with spider pictures in spider phobia

Facilitated detection of threatening visual cues is thought to be adaptive. In theory, detection of threat cues should activate the amygdala independently from allocation of attention. However, previous studies using emotional facial expressions as well as phobic cues yielded contradictory results. We used fMRI to examine whether the allocation of attention to components of superimposed spider and bird displays modulates amygdala activation. Nineteen spider-phobic women were instructed to identify either a moving or a stationary animal in briefly presented double-exposure displays. Amygdala activation followed a dose–response relationship: Compared to congruent neutral displays (two birds), amygdala activation was most pronounced in response to congruent phobic displays (two spiders) and less but still significant in response to mixed displays (spider and bird) when attention was focused on the phobic component. When attention was focused on the neutral component, mixed displays did not result in significant amygdala activation. This was confirmed in a significant parametric graduation of the amygdala activation in the order of congruent phobic displays, mixed displays with attention focus on the spider, mixed displays with focus on the bird and congruent neutral displays. These results challenge the notion that amygdala activation in response to briefly presented phobic cues is independent from attention.

Behavioral and genetic correlates of the neural response to infant crying among human fathers

Although evolution has shaped human infant crying and the corresponding response from caregivers, there is marked variation in paternal involvement and caretaking behavior, highlighting the importance of understanding the neurobiology supporting optimal paternal responses to cries. We explored the neural response to infant cries in fathers of children aged 1–2, and its relationship with hormone levels, variation in the androgen receptor (AR) gene, parental attitudes and parental behavior. Although number of AR CAG trinucleotide repeats was positively correlated with neural activity in brain regions important for empathy (anterior insula and inferior frontal gyrus), restrictive attitudes were inversely correlated with neural activity in these regions and with regions involved with emotion regulation (orbitofrontal cortex). Anterior insula activity had a non-linear relationship with paternal caregiving, such that fathers with intermediate activation were most involved. These results suggest that restrictive attitudes may be associated with decreased empathy and emotion regulation in response to a child in distress, and that moderate anterior insula activity reflects an optimal level of arousal that supports engaged fathering.     

Insular and hippocampal contributions to remembering people with an impression of bad personality

Our impressions of other people are formed mainly from the two possible factors of facial attractiveness and trustworthiness. Previous studies have shown the importance of orbitofrontal–hippocampal interactions in the better remembering of attractive faces, and psychological data have indicated that faces giving an impression of untrustworthiness are remembered more accurately than those giving an impression of trustworthiness. However, the neural mechanisms of the latter effect are largely unknown. To investigate this issue, we investigated neural activities with event-related fMRI while the female participants rated their impressions of the personalities of men in terms of trustworthiness. After the rating, memory for faces was tested to identify successful encoding activity. As expected, faces that gave bad impressions were remembered better than those that gave neutral or good impressions. In fMRI data, right insular activity reflected an increasing function of bad impressions, and bilateral hippocampal activities predicted subsequent memory success. Additionally, correlation between these insular and hippocampal regions was significant only in the encoding of faces associated with a bad impression. Better memory for faces associated with an impression of bad personality could reflect greater interaction between the avoidance-related insular region and the encoding-related hippocampal region.     

Relation of obesity to neural activation in response to food commercials

Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors.     

Effect of task conditions on brain responses to threatening faces in social phobics: an event-related functional magnetic resonance imaging study.

BACKGROUND: The aim of this study was to identify brain activation to socially threatening stimuli in social phobic subjects during different experimental conditions. METHODS: With event-related functional magnetic resonance imaging, brain activation to photographs and schematic pictures depicting angry or neutral facial expressions was measured in social phobic subjects and healthy control subjects, while subjects assessed either emotional expression (angry vs. neutral; explicit task) or picture type (photographic vs. schematic; implicit task). RESULTS: Compared with control subjects, phobics showed greater responses to angry than to neutral photographic faces in the insula regardless of task, whereas amygdala, parahippocampal gyrus, and extrastriate visual cortex were more strongly activated only during the implicit task. Phobics, in contrast to control subjects, showed similar activation patterns during both tasks. For schematic angry versus neutral faces, activation of insula and extrastriate visual cortex was found in phobics, but not in control subjects, during both tasks. CONCLUSIONS: Differences between social phobics and control subjects in brain responses to socially threatening faces are most pronounced when facial expression is task-irrelevant. Phobics intensively process angry (photographic as well as schematic) facial expressions, regardless of whether this is required. The insula plays a unique role in the processing of threat signals by social phobics.     

A preliminary study of orbitofrontal activation and hypersociability in Williams Syndrome

Individuals with Williams syndrome (WS) demonstrate an abnormally positive social bias. However, the neural substrates of this hypersociability, i.e., positive attribution bias and increased drive toward social interaction, have not fully been elucidated. METHODS: We performed an event-related functional magnetic resonance imaging study while individuals with WS and typically developing controls (TD) matched positive and negative emotional faces. WS compared to TD showed reduced right amygdala activation during presentation of negative faces, as in the previous literature. In addition, WS showed a unique pattern of right orbitofrontal cortex activation. While TD showed medial orbitofrontal cortex activation in response to positive, and lateral orbitofrontal cortex activation to negative, WS showed the opposite pattern. In light of the general notion of a medial/lateral gradient of reward/punishment processing in the orbitofrontal cortex, these findings provide an additional biological explanation for, or correlate of positive attribution bias and hypersociability in WS.     

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.     

抑郁症患者情绪图片反应特征及杏仁核反应模式的研究

目的 探讨抑郁症患者对情感刺激的行为学反应模式及其相关的杏仁核时程反应过程.方法 12例首次发病、未经治疗的抑郁症患者(抑郁症组)和13名健康个体(健康对照组)对观看正性、中性和负性情绪图片的愉悦度等评分;并在被动注视任务下行功能磁共振成像,采用感兴趣区分析方法,比较两组杏仁核在不同情绪图片任务组块间的血氧水平依赖(BOLD)信号时间反应特征.结果 (1)抑郁症组情绪图片愉悦度评分[正性:(6.6 ±0.2)分;中性:(4.7 ±0.1)分]低于健康对照组[分别为(7.7 ±0.2)分和(5.1 ±0.1)分],负性情绪图片评分[(3.4 ±0.3)分]高于健康对照组[(2.2 ±0.2)分;P<0.01].(2)对正性情绪图片任务,两组间右侧杏仁核存在"组×时间"交互作用(P=0.002);抑郁症组杏仁核BOLD信号变化率为(0.02±0.09)%,激活时间后移至Block 2.对负性情绪图片任务,两组间左侧杏仁核有"组×时间"交互作用(P=0.008),右侧杏仁核存在组主效应(P=0.007)和时间主效应(P=0.016),抑郁症组BOLD信号变化率低于(-0.06 ±0.14)%.结论 杏仁核是抑郁症患者丧失愉悦体验和情绪低落的神经基础之一.     

Brain activation by disgust-inducing pictures in obsessive-compulsive disorder.

BACKGROUND: There is growing interest in the role of disgust in the pathogenesis of obsessive-compulsive disorder (OCD). METHODS: Eight OCD subjects with contamination preoccupations and eight gender- and age-matched healthy volunteers viewed pictures from the International Affective Picture System during functional magnetic resonance imaging scans. RESULTS: A different distribution of brain activations was found during disgust-inducing visual stimulation in several areas, most notably the insula, compared with neutral stimulation in both OCD subjects and healthy volunteers. Furthermore, whereas activation during the threat-inducing task in OCD subjects showed a pattern similar to that in healthy volunteers, the pattern of activation during the disgust-inducing task was significantly different, including greater increases in the right insula, parahippocampal region, and inferior frontal sites. CONCLUSIONS: This pilot study supports the relevance of disgust in the neurocircuitry of OCD with contamination-preoccupation symptoms; future studies looking at non-OCD individuals with high disgust ratings, non-contamination-preoccupied OCD individuals, and individuals with other anxiety disorders are needed.     

The changing face of emotion: age-related patterns of amygdala activation to salient faces

The present study investigated age-related differences in the amygdala and other nodes of face-processing networks in response to facial expression and familiarity. fMRI data were analyzed from 31 children (3.5–8.5 years) and 14 young adults (18–33 years) who viewed pictures of familiar (mothers) and unfamiliar emotional faces. Results showed that amygdala activation for faces over a scrambled image baseline increased with age. Children, but not adults, showed greater amygdala activation to happy than angry faces; in addition, amygdala activation for angry faces increased with age. In keeping with growing evidence of a positivity bias in young children, our data suggest that children find happy faces to be more salient or meaningful than angry faces. Both children and adults showed preferential activation to mothers’ over strangers’ faces in a region of rostral anterior cingulate cortex associated with self-evaluation, suggesting that some nodes in frontal evaluative networks are active early in development. This study presents novel data on neural correlates of face processing in childhood and indicates that preferential amygdala activation for emotional expressions changes with age.     

Disrupted theory of mind network processing in response to idea of reference evocation in schizophrenia

Park IH, Ku J, Lee H, Kim SY, Kim SI, Yoon KJ, Kim J‐J. Disrupted theory of mind network processing in response to idea of reference evocation in schizophrenia. Objective: This study examined the neural pathophysiology of the theory of mind network by eliciting self‐referential processing during an idea of reference evocating situation in patients with schizophrenia. Method: Functional MRI was conducted on 14 schizophrenic in‐patients with the idea of reference and 15 healthy participants while viewing video vignettes of referential conversations, non‐referential conversations or no conversations between two people, which were filmed at varying distances of 1, 5 or 10 m. Results: The patient group did not show normal patterns of superior temporal sulcus activation to conversational context, and reciprocal deactivation and activation of the ventromedial and dorsomedial prefrontal cortex to referential conversational context. Instead, the patient group showed overall greater ventromedial prefrontal activities across different conversational contexts and inverse correlation between superior temporal sulcus activity and delusional severity. Differential activations of the temporal pole and its posterior extension to varying distances were observed in the control group but not in the patient group. Conclusion: The present study demonstrates that theory of mind‐related responses of the medial prefrontal‐superior temporal network are attenuated during the self‐referential processing in patients with schizophrenia and that these abnormalities may be related to the formation of their referential or persecutory delusion.