Cumulative activation during positive and negative events and state anxiety predicts subsequent inertia of amygdala reactivity

Inertia, together with intensity and valence, is an important component of emotion. We tested whether positive and negative events generate lingering changes in subsequent brain responses to unrelated threat stimuli and investigated the impact of individual anxiety. We acquired fMRI data while participants watched positive or negative movie-clips and subsequently performed an unrelated task with fearful and neutral faces. We quantified changes in amygdala reactivity to fearful faces as a function of the valence of preceding movies and cumulative neural activity evoked during them. We demonstrate that amygdala responses to emotional movies spill over to subsequent processing of threat information in a valence-specific manner: negative movies enhance later amygdala activation whereas positive movies attenuate it. Critically, the magnitude of such changes is predicted by a measure of cumulative amygdala responses to the preceding positive or negative movies. These effects appear independent of overt attention, are regionally limited to amygdala, with no changes in functional connectivity. Finally, individuals with higher state anxiety displayed stronger modulation of amygdala reactivity by positive movies. These results suggest that intensity and valence of emotional events as well as anxiety levels promote local changes in amygdala sensitivity to threat, highlighting the importance of past experience in shaping future affective reactivity.     

Emotion perception and executive control interact in the salience network during emotionally charged working memory processing

Processing of emotional stimuli can either hinder or facilitate ongoing working memory (WM); however, the neural basis of these effects remains largely unknown. Here we examined the neural mechanisms of these paradoxical effects by implementing a novel emotional WM task in an fMRI study. Twenty‐five young healthy participants performed an N‐back task with fearful and neutral faces as stimuli. Participants made more errors when performing 0‐back task with fearful versus neutral faces, whereas they made fewer errors when performing 2‐back task with fearful versus neutral faces. These emotional impairment and enhancement on behavioral performance paralleled significant interactions in distributed regions in the salience network including anterior insula (AI) and dorsal cingulate cortex (dACC), as well as in emotion perception network including amygdala and temporal‐occipital association cortex (TOC). The dorsal AI (dAI) and dACC were more activated when comparing fearful with neutral faces in 0‐back task. Contrarily, dAI showed reduced activation, while TOC and amygdala showed stronger responses to fearful as compared to neutral faces in the 2‐back task. These findings provide direct neural evidence to the emerging dual competition model suggesting that the salience network plays a critical role in mediating interaction between emotion perception and executive control when facing ever‐changing behavioral demands. Hum Brain Mapp 35:5606–5616, 2014. © 2014 Wiley Periodicals, Inc.     

Citalopram modulation of neuronal responses to aversive face emotions: a functional MRI study

This study investigated the serotonergic modulation of face emotion processing using blood oxygen level-dependent (BOLD) functional MRI. In a placebo-controlled, balanced order design, intravenous citalopram (7.5 mg) was given to 12 male volunteers 60 min before a covert face emotion recognition task. Angry, disgusted and fearful faces produced BOLD signal responses, which were broadly consistent with previous findings. Citalopram enhanced the BOLD signal response in the left posterior insula (together with nonprespecified pulvinar and visual cortex) but attenuated activation in the left amygdala to disgusted faces and right amygdala activation to fearful faces. No citalopram modulation of BOLD responses to angry faces were found. These results suggest that serotonin modulates low-level amygdala activation to aversive stimuli.     

Reduced electrocortical response to threatening faces in major depressive disorder

Background: There is growing support for the emotion context insensitivity hypothesis, which states that major depressive disorder (MDD) is associated with a deficit in emotional reactivity. Under this hypothesis, depressed individuals exhibit reduced behavioral and physiological responses to both appetitive and aversive stimuli. We sought to examine this possibility using the late positive potential, a neural response sensitive to aversive and threatening stimuli. Methods: Forty‐seven individuals participated in the study, 22 of whom met criteria for current MDD and 25 with no history of depression or other Axis I disorders. All individuals passively viewed emotional faces while event‐related potentials were recorded. Results: The vertex positive potential was significantly increased in response to fearful and angry faces across the entire sample. The late positive potential was also increased in response to threatening faces, but only among never‐depressed individuals. In the MDD group, this electrocortical response to emotional faces was absent. Conclusions: This study provides neural evidence in support of the view that MDD is associated with blunted emotional reactivity to negative stimuli, which until now has been examined primarily with measures of behavior, self‐report, and peripheral physiology. These results are also consistent with two prior studies showing reduced amygdala activation in response to fearful faces among depressed individuals. It remains to be determined whether abnormal activity in response to emotional stimuli is associated with trait risk for MDD or results from MDD. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

Emotion and personal space: Neural correlates of approach‐avoidance tendencies to different facial expressions as a function of coldhearted psychopathic traits

In social interactions, humans are expected to regulate interpersonal distance in response to the emotion displayed by others. Yet, the neural mechanisms implicated in approach‐avoidance tendencies to distinct emotional expressions have not been fully described. Here, we investigated the neural systems implicated in regulating the distance to different emotions, and how they vary as a function of empathy. Twenty‐three healthy participants assessed for psychopathic traits underwent fMRI scanning while they viewed approaching and withdrawing angry, fearful, happy, sad and neutral faces. Participants were also asked to set the distance to those faces on a computer screen, and to adjust the physical distance from the experimenter outside the scanner. Participants kept the greatest distances from angry faces, and shortest from happy expressions. This was accompanied by increased activation in the dorsomedial prefrontal and orbitofrontal cortices, inferior frontal gyrus, and temporoparietal junction for angry and happy expressions relative to the other emotions. Irrespective of emotion, longer distances were kept from approaching faces, which was associated with increased activation in the amygdala and insula, as well as parietal and prefrontal regions. Amygdala activation was positively correlated with greater preferred distances to angry, fearful and sad expressions. Moreover, participants scoring higher on coldhearted psychopathic traits (lower empathy) showed reduced amygdala activation to sad expressions. These findings elucidate the neural mechanisms underlying social approach‐avoidance, and how they are related to variations in empathy. Hum Brain Mapp 38:1492–1506, 2017. © 2016 Wiley Periodicals, Inc.     

5‐HTTLPR differentially predicts brain network responses to emotional faces

The effects of the 5‐HTTLPR polymorphism on neural responses to emotionally salient faces have been studied extensively, focusing on amygdala reactivity and amygdala‐prefrontal interactions. Despite compelling evidence that emotional face paradigms engage a distributed network of brain regions involved in emotion, cognitive and visual processing, less is known about 5‐HTTLPR effects on broader network responses. To address this, we evaluated 5‐HTTLPR differences in the whole‐brain response to an emotional faces paradigm including neutral, angry and fearful faces using functional magnetic resonance imaging in 76 healthy adults. We observed robust increased response to emotional faces in the amygdala, hippocampus, caudate, fusiform gyrus, superior temporal sulcus and lateral prefrontal and occipito‐parietal cortices. We observed dissociation between 5‐HTTLPR groups such that L_AL_A individuals had increased response to only angry faces, relative to neutral ones, but S′ carriers had increased activity for both angry and fearful faces relative to neutral. Additionally, the response to angry faces was significantly greater in L_AL_A individuals compared to S′ carriers and the response to fearful faces was significantly greater in S′ carriers compared to L_AL_A individuals. These findings provide novel evidence for emotion‐specific 5‐HTTLPR effects on the response of a distributed set of brain regions including areas responsive to emotionally salient stimuli and critical components of the face‐processing network. These findings provide additional insight into neurobiological mechanisms through which 5‐HTTLPR genotype may affect personality and related risk for neuropsychiatric illness. Hum Brain Mapp 36:2842–2851, 2015. © 2015 Wiley Periodicals, Inc.     

Amygdala hyperactivation to angry faces in intermittent explosive disorder

BackgroundIndividuals with intermittent explosive disorder (IED) were previously found to exhibit amygdala hyperactivation and relatively reduced orbital medial prefrontal cortex (OMPFC) activation to angry faces while performing an implicit emotion information processing task during functional magnetic resonance imaging (fMRI). This study examines the neural substrates associated with explicit encoding of facial emotions among individuals with IED.MethodTwenty unmedicated IED subjects and twenty healthy, matched comparison subjects (HC) underwent fMRI while viewing blocks of angry, happy, and neutral faces and identifying the emotional valence of each face (positive, negative or neutral). We compared amygdala and OMPFC reactivity to faces between IED and HC subjects. We also examined the relationship between amygdala/OMPFC activation and aggression severity.ResultsCompared to controls, the IED group exhibited greater amygdala response to angry (vs. neutral) facial expressions. In contrast, IED and control groups did not differ in OMPFC activation to angry faces. Across subjects amygdala activation to angry faces was correlated with number of prior aggressive acts.ConclusionsThese findings extend previous evidence of amygdala dysfunction in response to the identification of an ecologically-valid social threat signal (processing angry faces) among individuals with IED, further substantiating a link between amygdala hyperactivity to social signals of direct threat and aggression.     

Age‐related changes in amygdala–frontal connectivity during emotional face processing from childhood into young adulthood

The ability to process and respond to emotional facial expressions is a critical skill for healthy social and emotional development. There has been growing interest in understanding the neural circuitry underlying development of emotional processing, with previous research implicating functional connectivity between amygdala and frontal regions. However, existing work has focused on threatening emotional faces, raising questions regarding the extent to which these developmental patterns are specific to threat or to emotional face processing more broadly. In the current study, we examined age‐related changes in brain activity and amygdala functional connectivity during an fMRI emotional face matching task (including angry, fearful, and happy faces) in 61 healthy subjects aged 7–25 years. We found age‐related decreases in ventral medial prefrontal cortex activity in response to happy faces but not to angry or fearful faces, and an age‐related change (shifting from positive to negative correlation) in amygdala–anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) functional connectivity to all emotional faces. Specifically, positive correlations between amygdala and ACC/mPFC in children changed to negative correlations in adults, which may suggest early emergence of bottom‐up amygdala excitatory signaling to ACC/mPFC in children and later development of top‐down inhibitory control of ACC/mPFC over amygdala in adults. Age‐related changes in amygdala–ACC/mPFC connectivity did not vary for processing of different facial emotions, suggesting changes in amygdala–ACC/mPFC connectivity may underlie development of broad emotional processing, rather than threat‐specific processing. Hum Brain Mapp 37:1684–1695, 2016. © 2016 Wiley Periodicals, Inc .     

Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study.

BACKGROUND: The amygdala has a central role in processing emotions, particularly fear. During functional magnetic resonance imaging (fMRI) amygdala activation has been demonstrated outside of conscious awareness using masked emotional faces. METHODS: We applied the masked faces paradigm to patients with major depression (n = 11) and matched control subjects (n = 11) during fMRI to compare amygdala activation in response to masked emotional faces before and after antidepressant treatment. Data were analyzed using left and right amygdala a priori regions of interest, in an analysis of variance block analysis and random effects model. RESULTS: Depressed patients had exaggerated left amygdala activation to all faces, greater for fearful faces. Right amygdala did not differ from control subjects. Following treatment, patients had bilateral reduced amygdala activation to masked fearful faces and bilateral reduced amygdala activation to all faces. Control subjects had no differences between the two scanning sessions. CONCLUSIONS: Depressed patients have left amygdala hyperarousal, even when processing stimuli outside conscious awareness. Increased amygdala activation normalizes with antidepressant treatment.     

Amygdalar activation associated with positive and negative facial expressions

Most theories of amygdalar function have underscored its role in fear. One broader theory suggests that neuronal activation of the amygdala in response to fear-related stimuli represents only a portion of its more widespread role in modulating an organism's vigilance level. To further explore this theory, the amygdalar response to happy, sad, angry, fearful, and neutral faces in 17 subjects was characterized using 3 T fMRI. Utilizing a random effects model and hypothesis-driven analytic strategy, it was observed that each of the four emotional faces was associated with reliable bilateral activation of the amygdala compared with neutral. These findings suggest a broader role for the amygdala in modulating the vigilance level during the perception of several negative and positive facial emotions.     

Mismatch negativity (MMN) stands at the crossroads between explicit and implicit emotional processing

The amygdala is known as a key brain region involved in the explicit and implicit processing of emotional faces, and plays a crucial role in salience detection. Not until recently was the mismatch negativity (MMN), a component of the event‐related potentials to an odd stimulus in a sequence of stimuli, utilized as an index of preattentive salience detection of emotional voice processing. However, their relationship remains to be delineated. This study combined the fMRI scanning and event‐related potential recording by examining amygdala reactivity in response to explicit and implicit (backward masked) perception of fearful and angry faces, along with recording MMN in response to the fearfully and angrily spoken syllables dada in healthy subjects who varied in trait anxiety (STAI‐T). Results indicated that the amplitudes of fearful MMN were positively correlated with left amygdala reactivity to explicit perception of fear, but negatively correlated with right amygdala reactivity to implicit perception of fear. The fearful MMN predicted STAI‐T along with left amygdala reactivity to explicit fear, whereas the association between fearful MMN and STAI‐T was mediated by right amygdala reactivity to implicit fear. These findings suggest that amygdala reactivity in response to explicit and implicit threatening faces exhibits opposite associations with emotional MMN. In terms of emotional processing, MMN not only reflects preattentive saliency detection but also stands at the crossroads of explicit and implicit perception. Hum Brain Mapp 38:140–150, 2017. © 2016 Wiley Periodicals, Inc.     

Increased amygdala activation to angry and contemptuous faces in generalized social phobia

BACKGROUND: Generalized social phobia (GSP) is characterized by fear of social interactions and sensitivity to disapproval by others. Given the established role of the amygdala as part of a distributed neural system for the processing of emotional cues, we hypothesized that subjects with GSP would exhibit greater amygdala activation in response to harsh (angry, fearful, and contemptous) vs accepting (happy) facial emotional expressions compared with healthy control subjects (HCs). METHODS: Fifteen subjects with DSM-IV GSP and 15 age-, sex-, handedness-, and education-matched HCs, free of psychotropic medication for at least 12 weeks, viewed 60 color photographs from a standardized set of human facial stimuli, during which the task was to identify the sex of the person in the photograph. Data were collected across 3 functional (echo-planar) runs using a Siemens 1.5-T magnet, and analyzed using Analysis of Functional Neuroimaging software (Medical College of Wisconsin, Milwaukee). RESULTS: In the left allocortex (including the amygdala, uncus, and parahippocampal gyrus), subjects with GSP produced a significantly greater percent blood oxygen level-dependent signal change than did HCs for contemptous compared with happy faces (GSP: 0.72% vs HC: -0.01%; F(1,29) = 9.56, P =.004, Cohen d = 1.15) and for angry compared with happy faces (GSP: 0.45% vs HC: -0.09%; F(1,29) = 6.78, P =.02, Cohen d = 1.00). Subjects with GSP and HCs did not produce a statistically different percent signal change for fearful or nonexpressive faces compared with the happy faces in this region. CONCLUSIONS: These findings are consistent with a role for differential amygdala (and associated limbic) functioning in GSP. The pronounced response to contemptuous and angry facial expressions suggests that the amygdala in GSP may be particularly active in the processing of disorder-salient stimuli.     

Preferential responses to faces in superior temporal and medial prefrontal cortex in three-year-old children

Perceiving faces and understanding emotions are key components of human social cognition. Prior research with adults and infants suggests that these social cognitive functions are supported by superior temporal cortex (STC) and medial prefrontal cortex (MPFC). We used functional near-infrared spectroscopy (fNIRS) to characterize functional responses in these cortical regions to faces in early childhood. Three-year-old children (n = 88, M(SD) = 3.15(.16) years) passively viewed faces that varied in emotional content and valence (happy, angry, fearful, neutral) and, for fearful and angry faces, intensity (100%, 40%), while undergoing fNIRS. Bilateral STC and MPFC showed greater oxygenated hemoglobin concentration values to all faces relative to objects. MPFC additionally responded preferentially to happy faces relative to neutral faces. We did not detect preferential responses to angry or fearful faces, or overall differences in response magnitude by emotional valence (100% happy vs. fearful and angry) or intensity (100% vs. 40% fearful and angry). In exploratory analyses, preferential responses to faces in MPFC were not robustly correlated with performance on tasks of early social cognition. These results link and extend adult and infant research on functional responses to faces in STC and MPFC and contribute to the characterization of the neural correlates of early social cognition.     

A developmental examination of gender differences in brain engagement during evaluation of threat.

BACKGROUND: Females appear to be more sensitive and responsive to social cues, including threat signals, than are males. Recent theoretical models suggest that developmental changes in brain functioning play important roles in the emergence of such gender differences. METHODS: We used functional magnetic resonance imaging to examine developmental and gender differences in activation of neural structures thought to mediate attention to emotional faces depicting varying degrees of threat. Analyses focused on the orbitofrontal cortex, amygdala, and anterior cingulate cortex during the evaluation of threat conveyed by faces. Healthy adolescents (n = 17; 53% male) and adults (n = 17; 53% male) were scanned while they rated how threatening pictures of neutral and emotional (angry, fearful, or happy) faces appeared. RESULTS: Results indicate significant interactions among age, gender, and face type for activation during explicit threat monitoring. In particular, adult women activated orbitofrontal cortex and amygdala selectively to unambiguous threat (angry) cues, while adult men showed a less discriminating pattern of activation. No gender differences were evident for adolescents, who as a group resembled adult males. CONCLUSIONS: These findings suggest that there are gender differences in patterns of neural responses to emotional faces that are not fully apparent until adulthood.     

Children's processing of emotions expressed by peers and adults: An fMRI study

The recognition of emotional expressions is an important skill and relates to social functioning and adjustment in childhood. The current functional MRI study investigated the neural processing of angry and happy facial expressions in 5- to 6-year-old children and in adults. Participants were presented happy and angry faces of adults and children while they performed a non-emotion-related task with low cognitive load. Very similar neural networks were involved in the processing of angry and happy faces in adults and children, including the amygdala and prefrontal areas. In general, children showed heightened amygdala activation in response to emotional faces relative to adults. While children showed stronger amygdala activation in response to angry adult compared to angry child faces, adults showed stronger amygdala activation for angry child faces. In both age groups enhanced amygdala involvement was found for happy peer faces relative to happy non-peer faces, though this effect was only a tendency in adults. The findings are discussed in the context of the development of the social brain network.     

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.     

Neural responses to happy,fearful and angry faces of varying identities in 5- and 7-month-old infants

The processing of facial emotion is an important social skill that develops throughout infancy and early childhood. Here we investigate the neural underpinnings of the ability to process facial emotion across changes in facial identity in cross-sectional groups of 5- and 7-month-old infants. We simultaneously measured neural metabolic, behavioral, and autonomic responses to happy, fearful, and angry faces of different female models using functional near-infrared spectroscopy (fNIRS), eye-tracking, and heart rate measures. We observed significant neural activation to these facial emotions in a distributed set of frontal and temporal brain regions, and longer looking to the mouth region of angry faces compared to happy and fearful faces. No differences in looking behavior or neural activations were observed between 5- and 7-month-olds, although several exploratory, age-independent associations between neural activations and looking behavior were noted. Overall, these findings suggest more developmental stability than previously thought in responses to emotional facial expressions of varying identities between 5- and 7-months of age.     

Amygdala and nucleus accumbens activation to emotional facial expressions in children and adolescents at risk for major depression

OBJECTIVE: Offspring of parents with major depressive disorder face a threefold higher risk for major depression than offspring without such family histories. Although major depression is a significant cause of morbidity and mortality, neural correlates of risk for major depression remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for major depression under varying attentional and emotional conditions. METHOD: Thirty-nine juveniles, 17 offspring of parents with major depression (high-risk group) and 22 offspring of parents without histories of major depression, anxiety, or psychotic disorders (low-risk group) completed a functional magnetic resonance imaging study. During imaging, subjects viewed faces that varied in intensity of emotional expressions across blocks of trials while attention was unconstrained (passive viewing) and constrained (rate nose width on face, rate subjective fear while viewing face). RESULTS: When attention was unconstrained, high-risk subjects showed greater amygdala and nucleus accumbens activation to fearful faces and lower nucleus accumbens activation to happy faces (small volume corrected for the amygdala and nucleus accumbens). No group differences emerged in amygdala or nucleus accumbens activation during constrained attention. Exploratory analysis showed that constraining attention was associated with greater medial prefrontal cortex activation in the high-risk than in the low-risk group. CONCLUSIONS: Amygdala and nucleus accumbens responses to affective stimuli may reflect vulnerability for major depression. Constraining attention may normalize emotion-related neural function possibly by engagement of the medial prefrontal cortex; face-viewing with unconstrained attention may engage aberrant processes associated with risk for major depression.     

1 hz rTMS over the right prefrontal cortex reduces vigilant attention to unmasked but not to masked fearful faces.

BACKGROUND: Recent repetitive transcranial magnetic stimulation (rTMS) research in healthy subjects suggests that the emotions anger and anxiety are lateralized in the prefrontal cortex. Low-frequency rTMS over the right prefrontal cortex (PFC) shifts the anterior asymmetry in brain activation to the left hemisphere and reduces anxiety. The same rTMS technique results in enhanced anger-related emotional processing, observed as elevations in attention for angry faces. The current study used low-frequency rTMS over the right PFC and indexed selective attention to fearful faces, hypothesizing a reduction in attention for fearful faces, i.e., a reversal of the latter effect. METHODS: In a placebo-controlled design, 1 Hz rTMS at 130% of the individual motor threshold (MT) was applied continuously over the right PFC of eight healthy subjects for 20 minutes. Effects on motivated attention were investigated by means of an emotional Stroop task, indexing selective attention to masked and unmasked fearful faces. RESULTS: Vigilant attention for masked and unmasked fearful faces was observed after placebo stimulation. As hypothesized, rTMS reduced the vigilant emotional response to the fearful face, but only in the unmasked task. CONCLUSIONS: These data provide further support for the lateralization of the emotions anger and anxiety in the prefrontal cortex. In addition, the absence of an effect for masked fearful faces suggests that changes in emotional processing after a single session of rTMS predominantly involve the cortical affective pathways.     

Feature-based representations of emotional facial expressions in the human amygdala

The amygdala plays a central role in processing facial affect, responding to diverse expressions and features shared between expressions. Although speculation exists regarding the nature of relationships between expression- and feature-specific amygdala reactivity, this matter has not been fully explored. We used functional magnetic resonance imaging and principal component analysis (PCA) in a sample of 300 young adults, to investigate patterns related to expression- and feature-specific amygdala reactivity to faces displaying neutral, fearful, angry or surprised expressions. The PCA revealed a two-dimensional correlation structure that distinguished emotional categories. The first principal component separated neutral and surprised from fearful and angry expressions, whereas the second principal component separated neutral and angry from fearful and surprised expressions. This two-dimensional correlation structure of amygdala reactivity may represent specific feature-based cues conserved across discrete expressions. To delineate which feature-based cues characterized this pattern, face stimuli were averaged and then subtracted according to their principal component loadings. The first principal component corresponded to displacement of the eyebrows, whereas the second principal component corresponded to increased exposure of eye whites together with movement of the brow. Our results suggest a convergent representation of facial affect in the amygdala reflecting feature-based processing of discrete expressions.