Clinical hallmarks of borderline personality disorder (BPD) include social and emotional dysregulation. We tested a model of frontolimbic dysfunction in facial emotion processing in BPD. Groups of 12 unmedicated adults with BPD by DSM-IV and 12 demographically-matched healthy controls (HC) viewed facial expressions (Conditions) of neutral emotion, fear and anger, and made gender discriminations during rapid event-related functional magnetic resonance imaging (fMRI). Analysis of variance of Region of Interest signal change revealed a statistically significant effect of the Group-by-Region-by-Condition interaction. This was due to the BPD group exhibiting a significantly larger magnitude of deactivation (relative to HC) in the bilateral rostral/subgenual anterior cingulate cortex (ACC) to fear and in the left ACC to fear minus neutral; and significantly greater activation in the right amygdala to fear minus neutral. There were no significant between-group differences in ROI signal change in response to anger. In voxel-wise analyses constrained within these ROIs, the BPD group exhibited significant changes in the fear minus neutral contrast, with relatively less activation in the bilateral rostral/subgenual ACC, and greater activation in the right amygdala. In the anger minus neutral contrast this pattern was reversed, with the BPD group showing greater activation in the bilateral rostral/subgenual ACC and less activation in the bilateral amygdala. We conclude that adults with BPD exhibit changes in fronto-limbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of ACC activity. The neural substrates underlying processing of anger may also be altered. These changes may represent an expression of the volumetric and serotonergic deficits observed in these brain areas in BPD.
anterior cingulate cortex; amygdala; fear; anger; functional magnetic resonance imaging
Emotion regulation is a critical aspect of children's social development, yet few studies have examined the brain mechanisms involved in the development of emotion regulation. Theoretical accounts have conceptualized emotion regulation as relying upon prefrontal control of limbic regions, specifying the anterior cingulate cortex (ACC) as a key brain region for the regulation of emotion. Functional magnetic resonance imaging (fMRI) in 5- to 11-year-olds during emotion regulation and processing of emotionally expressive faces revealed that older children preferentially recruited the more dorsal “cognitive” areas of the ACC, while younger children preferentially engaged the more ventral “emotional” areas. Additionally, children with more fearful temperaments exhibited more ventral ACC activity while less fearful children exhibited increased activity in the dorsal ACC. These findings provide insight into a potential neurobiological mechanism underlying well-documented behavioral and cognitive changes from more emotional to more cognitive regulatory strategies with increasing age, as well as individual differences in this developmental process as a function of temperament. Our results hold important implications for our understanding of normal development and should also help to inform our understanding and management of emotional disorders.
Emotion Regulation; Development; fMRI; Anterior Cingulate; Temperament
Filmmakers have long recognized the importance of editing techniques to guide the audiences' perceptions and enhance the impact of a scene. We demonstrate behaviorally that pairing identical faces with either neutral or emotionally salient contextual movies, an editing technique referred to as the ‘Kuleshov Effect’, results in both altered attributions of facial expression and mental-state. Using functional neuroimaging (fMRI), we show that faces paired with emotional movies enhance BOLD responses in the bilateral temporal pole, anterior cingulate cortices, amygdala and bilateral superior temporal sulcus relative to identical faces juxtaposed with neutral movies. An interaction was observed in the right amygdala when subtle happy and fear faces were juxtaposed with positive and negative movies, respectively. An interaction between happy faces and negative context was also observed in bilateral amygdala suggesting that the amygdala may act to prime or tag affective value to faces. A parametric modulation of BOLD signal by attribution ratings indicated a dissociation between ventrolateral and the ventromedial prefrontal cortex for negative and positive contextually evoked attributions, respectively. These prefrontal regions may act to guide appropriate choices across altering contexts. Together, these findings offer a neurobiological basis for contextual framing effects on social attributions.
fMRI; kuleshov effect; context; affect; mental-state
Filmmakers have long recognized the importance of editing techniques to guide the audiences' perceptions and enhance the impact of a scene. We demonstrate behaviorally that pairing identical faces with either neutral or emotionally salient contextual movies, an editing technique referred to as the 'Kuleshov Effect', results in both altered attributions of facial expression and mental-state. Using functional neuroimaging (fMRI), we show that faces paired with emotional movies enhance BOLD responses in the bilateral temporal pole, anterior cingulate cortices, amygdala and bilateral superior temporal sulcus relative to identical faces juxtaposed with neutral movies. An interaction was observed in the right amygdala when subtle happy and fear faces were juxtaposed with positive and negative movies, respectively. An interaction between happy faces and negative context was also observed in bilateral amygdala suggesting that the amygdala may act to prime or tag affective value to faces. A parametric modulation of BOLD signal by attribution ratings indicated a dissociation between ventrolateral and the ventromedial prefrontal cortex for negative and positive contextually evoked attributions, respectively. These prefrontal regions may act to guide appropriate choices across altering contexts. Together, these findings offer a neurobiological basis for contextual framing effects on social attributions.
fMRI; kuleshov effect; context; affect; mental-state
Pregenual anterior cingulate cortex (pgACC) hyperactivity differentiates treatment responders from non-responders to various pharmacological antidepressant interventions, including ketamine, an N-methyl--aspartate receptor antagonist. Evidence of pgACC hyperactivition during non-emotional working memory tasks in patients with major depressive disorder (MDD) highlights the importance of this region for processing both emotionally salient and cognitive stimuli. However, it is unclear whether pgACC activity might serve as a potential biomarker of antidepressant response during working memory tasks as well, in line with previous research with emotionally arousing tasks. This study tested the hypothesis that during the N-back task, a widely used working memory paradigm, low pretreatment pgACC activity, as well as coherence between the pgACC and the amygdala, would be correlated with the clinical improvement after ketamine. Magnetoencephalography (MEG) recordings were obtained from 15 drug-free patients with MDD during working memory performance 1 to 3 days before receiving a single ketamine infusion. Functional activation patterns were analyzed using advanced MEG source analysis. Source coherence analyses were conducted to quantify the degree of long-range functional connectivity between the pgACC and the amygdala. Patients who showed the least engagement of the pgACC in response to increased working memory load showed the greatest symptomatic improvement within 4 h of ketamine administration (r=0.82, p=0.0002, false discovery rate (FDR) <0.05). Pretreatment functional connectivity between the pgACC and the left amygdala was negatively correlated with antidepressant symptom change (r=−0.73, p=0.0021, FDR <0.05).These data implicate the pgACC and its putative interaction with the amygdala in predicting antidepressant response to ketamine in a working memory task context.
major depressive disorder (MDD); magnetoencephalography (MEG); N-back; biomarker; beta desynchronization; Biological Psychiatry; Mood/Anxiety/Stress Disorders; Imaging; Clinical or Preclinical; Glutamate; magnetoencephalography; N-back; beta desynchronization; biomarker
Functional neuroimaging studies have largely established the prominence of amygdala during emotion processing and prefrontal areas such as anterior cingulate cortex (ACC) during attentional modulation. In general, emotion processing paradigms known to probe amygdala have not been adapted to recruit prefrontal areas. In this study we used a well-known perceptual face matching paradigm, designed to elicit amygdala response, and asked volunteers to shift their focus in order to recruit regions responsible for attentional control. Stimuli comprised a trio of geometric shapes (circles, rectangles, triangles) presented alongside a trio of emotional faces (angry, fear, or happy) within the same field of view, and subjects were instructed to Match Faces or Match Shapes, as a means of attending to and away from the emotional content, respectively. We observed greater amygdala reactivity to Match Faces (>Match Shapes), and greater rostral ACC response to Match Shapes (>Match Faces). Results indicate that simply and volitionally directing attention towards or away from emotional content correspondingly modulates amygdala and ACC activity.
The ability to process stimuli that convey potential threat, under conditions of limited attentional resources, confers adaptive advantages. This study examined the neurobiology underpinnings of this capacity. Employing an attentional blink paradigm, in conjunction with functional magnetic resonance imaging, we manipulated the salience of the second of 2 face target stimuli (T2), by varying emotionality. Behaviorally, fearful T2 faces were identified significantly more than neutral faces. Activity in fusiform face area increased with correct identification of T2 faces. Enhanced activity in rostral anterior cingulate cortex (rACC) accounted for the benefit in detection of fearful stimuli reflected in a significant interaction between target valence and correct identification. Thus, under conditions of limited attention resources activation in rACC correlated with enhanced processing of emotional stimuli. We suggest that these data support a model in which a prefrontal “gate” mechanism controls conscious access of emotional information under conditions of limited attentional resources.
attention; attentional blink; emotion; fMRI; fusiform face area; rACC
Emotion and reward have been proposed to be closely linked to conscious experience, but empirical data are lacking. The anterior cingulate cortex (ACC) plays a central role in the hedonic dimension of conscious experience; thus potentially a key region in interactions between emotion and consciousness. Here we tested the impact of emotion on conscious experience, and directly investigated the role of the ACC. We used a masked paradigm that measures conscious reportability in terms of subjective confidence and objective accuracy in identifying the briefly presented stimulus in a forced-choice test. By manipulating the emotional valence (positive, neutral, negative) and the presentation time (16 ms, 32 ms, 80 ms) we measured the impact of these variables on conscious and subliminal (i.e. below threshold) processing. First, we tested normal participants using face and word stimuli. Results showed that participants were more confident and accurate when consciously seeing happy versus sad/neutral faces and words. When stimuli were presented subliminally, we found no effect of emotion. To investigate the neural basis of this impact of emotion, we recorded local field potentials (LFPs) directly in the ACC in a chronic pain patient. Behavioural findings were replicated: the patient was more confident and accurate when (consciously) seeing happy versus sad faces, while no effect was seen in subliminal trials. Mirroring behavioural findings, we found significant differences in the LFPs after around 500 ms (lasting 30 ms) in conscious trials between happy and sad faces, while no effect was found in subliminal trials. We thus demonstrate a striking impact of emotion on conscious experience, with positive emotional stimuli enhancing conscious reportability. In line with previous studies, the data indicate a key role of the ACC, but goes beyond earlier work by providing the first direct evidence of interaction between emotion and conscious experience in the human ACC.
Pregenual anterior cingulate (pgACC) hyperactivity differentiates treatment responders from non-responders to various pharmacological antidepressant interventions, including ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist. Evidence of pgACC hyperactivition during non-emotional working memory tasks in patients with major depressive disorder (MDD) highlights the importance of this region for processing both emotionally-salient and cognitive stimuli. However, it is unclear whether pgACC activity might serve as a potential biomarker of antidepressant response during working memory tasks as well, in line with previous research with emotionally-arousing tasks. The present study tested the hypothesis that during the N-back task, a widely-used working memory paradigm, low pre-treatment pgACC activity, as well as coherence between the pgACC and the amygdala, would be correlated with the clinical improvement following ketamine.
Magnetoencephalography (MEG) recordings were obtained from 15 drug-free patients with MDD during working memory performance one to three days before receiving a single ketamine infusion. Functional activation patterns were analyzed using advanced MEG source analysis. Source coherence analyses were conducted to quantify the degree of long-range functional connectivity between the pgACC and the amygdala.
Patients who showed the least engagement of the pgACC in response to increased working memory load showed the greatest symptomatic improvement within four hours of ketamine administration (r = 0.82, p = 0.0002, FDR < 0.05). Pre-treatment functional connectivity between the pgACC and the left amygdala was negatively correlated with antidepressant symptom change (r = −0.73, p = 0.0021, FDR <0.05).
These data implicate the pgACC and its putative interaction with the amygdala in predicting antidepressant response to ketamine in a working memory task context.
major depressive disorder (MDD); magnetoencephalography (MEG); N-back; biomarker; beta desynchronization
Generalized social anxiety disorder (gSAD) is associated with a heightened neural sensitivity to signals that convey threat, as evidenced by exaggerated amygdala and/or insula activation when processing face stimuli that express negative emotions. Less clear in the brain pathophysiology of gSAD are cortical top down control mechanisms that moderate reactivity in these subcortical emotion processing regions. This study evaluated amygdala, insula, and anterior cingulate cortex (ACC) activity in gSAD with a novel “Emotional Faces Shifting Attention Task” (EFSAT), an adaptation of perceptual assessment tasks well-known to elicit amygdala response. In healthy volunteers, the task has been shown to engage the amygdala when attention is directed to emotional faces and the ACC when attention is directed to shapes, away from emotional faces.
During functional MRI, 29 participants with gSAD and 27 healthy controls viewed images comprising a trio of faces (angry, fear, or happy) alongside a trio of geometric shapes (circles, rectangles, or triangles) within the same field of view. Participants were instructed to match faces or match shapes, effectively directing attention towards or away from emotional information, respectively.
Participants with gSAD exhibited greater insula, but not amygdala, activation compared to controls when attending to emotional faces. In contrast, when attention was directed away from faces, controls exhibited ACC recruitment, which was not evident in gSAD. Across participants, greater ACC activation was associated with less insula activation.
Evidence that individuals with gSAD exhibited exaggerated insula reactivity when attending to emotional faces in EFSAT is consistent with other studies suggesting that the neural basis of gSAD may involve insula hyper-reactivity. Furthermore, greater ACC response in controls than gSAD when sustained goal-directed attention is required to shift attention away from social signals, together with a negative relationship between ACC and bilateral insula activity, indicate the ACC may have served a regulatory role when the focus of attention was directed to shapes amidst emotional faces.
Social anxiety; fMRI; Emotional faces; Threat processing; Brain imaging
Inability to modulate attention away from emotional stimuli may be a key component of dysregulated emotion in bipolar disorder (BD). Previous studies of BD indicate abnormalities in neural circuitry underlying attentional control, yet few studies examined attentional control in the context of emotional distracters. We compared activity and connectivity in neural circuitry supporting attentional control and emotion processing among 22 individuals with BD type 1, currently remitted and euthymic, and 19 healthy controls. Participants performed an emotional n-back paradigm, comprising high and low attentional demand conditions, each with either emotional (happy, fearful), neutral or no face flanker distracters. During the high attentional control demand conditions without emotional distracters, BD individuals showed reduced activity versus controls in dorsolateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and inferior parietal cortex. During the high attentional control demand conditions with fearful-face distracters, BD individuals showed greater activity than controls in these regions and amygdala and striatum. Relative to controls, BD individuals also showed abnormal patterns of effective connectivity between dACC and amygdala during high attentional control demand with emotional face distracters. Inter-episode bipolar disorder is characterized by abnormal recruitment of attentional control neural circuitry, especially in the context of emotionally distracting information.
magnetic resonance imaging; attention; working memory; emotion regulation; effective connectivity
Human faces provide important signals in social interactions by inferring two main types of information, individual identity and emotional expression. The ability to readily assess both, the variability and consistency among emotional expressions in different individuals, is central to one's own interpretation of the imminent environment. A factorial design was used to systematically test the interaction of either constant or variable emotional expressions with constant or variable facial identities in areas involved in face processing using functional magnetic resonance imaging.
Previous studies suggest a predominant role of the amygdala in the assessment of emotional variability. Here we extend this view by showing that this structure activated to faces with changing identities that display constant emotional expressions. Within this condition, amygdala activation was dependent on the type and intensity of displayed emotion, with significant responses to fearful expressions and, to a lesser extent so to neutral and happy expressions. In contrast, the lateral fusiform gyrus showed a binary pattern of increased activation to changing stimulus features while it was also differentially responsive to the intensity of displayed emotion when processing different facial identities.
These results suggest that the amygdala might serve to detect constant facial emotions in different individuals, complementing its established role for detecting emotional variability.
This study assessed the impact of serotonin transporter genotype (5-HTTLPR) on regional responses to emotional faces in the amygdala and subgenual cingulate cortex (sgACC), while subjects performed a gender discrimination task. Although we found no evidence for greater amygdala reactivity or reduced amygdala–sgACC coupling in short variant 5-HTTLPR homozygotes (s/s), we observed an interaction between genotype and emotion in sgACC. Only long variant homozygotes (la/la) exhibited subgenual deactivation to fearful versus neutral faces, whereas the effect in s/s subjects was in the other direction. This absence of subgenual deactivation in s/s subjects parallels a recent finding in depressed subjects [Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., Walter, M., et al. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology, 34, 932–943, 2009]. Taken together, the findings suggest that subgenual cingulate activity may play an important role in regulating the impact of aversive stimuli, potentially conferring greater resilience to the effects of aversive stimuli in la/la subjects. Using dynamic causal modeling of functional magnetic resonance imaging data, we explored the effects of genotype on effective connectivity and emotion-specific changes in coupling across a network of regions implicated in social processing. Viewing fearful faces enhanced bidirectional excitatory coupling between the amygdala and the fusiform gyrus, and increased the inhibitory influence of the amygdala over the sgACC, although this modulation of coupling did not differ between the genotype groups. The findings are discussed in relation to the role of sgACC and serotonin in moderating responses to aversive stimuli [Dayan, P., & Huys, Q. J., Serotonin, inhibition, and negative mood. PLoS Comput Biol, 4, e4, 2008; Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., et al. Reciprocal limbic–cortical function and negative mood: Converging PET findings in depression and normal sadness. Am J Psychiatry, 156, 675–682, 1999].
Autism spectrum disorders (ASD) involve a core deficit in social functioning and impairments in the ability to recognize face emotions. In an emotional faces task designed to constrain group differences in attention, the present study used functional MRI to characterize activation in the amygdala, ventral prefrontal cortex (vPFC), and striatum, three structures involved in socio-emotional processing, in adolescents with ASD.
Twenty-two adolescents with ASD and 20 healthy adolescents viewed facial expressions (happy, fearful, sad and neutral) that were briefly presented (250ms) during functional MRI acquisition. To monitor attention, subjects pressed a button to identify the gender of each face.
The ASD group showed greater activation to the faces relative to the control group in the amygdala, vPFC and striatum. Follow-up analyses indicated that the ASD relative to control group showed greater activation in the amygdala, vPFC and striatum (p<.05 small volume corrected), particularly to sad faces. Moreover, in the ASD group, there was a negative correlation between developmental variables (age and pubertal status) and mean activation from the whole bilateral amygdala; younger adolescents showed greater activation than older adolescents. There were no group differences in accuracy or reaction time in the gender identification task.
When group differences in attention to facial expressions were limited, adolescents with ASD showed greater activation in structures involved in socio-emotional processing.
Autism; Adolescents; FMRI; Faces; Emotion
Anterior cingulate cortex (ACC) is involved in emotion, emotional expression, mood and autonomic regulation in contrast to midcingulate cortex, which regulates response selection via cognitive and skeletomotor mechanisms. Although a subgenual part of ACC (sACC) may be vulnerable in depression and area 25 is cytologically unique, there are no assessments that contrast this region to pregenual ACC (pACC); both include parts of areas 32, 24, and 33 and the cingulate sulcus extends rostral to the corpus callosum and might contain area 24c. Independent verifications of cytoarchitectural differences among subregions, areas and laminar binding was undertaken with an observer-interactive approach and multireceptor autoradiography. Areas 24a and 24b have pregenual (p24a, p24b) and subgenual (s24a, s24b) components and subgenual areas have a very thin layer III. Area 24c is rostral to the genu (p24c) and has dorsal (pd24c) and ventral (pv24c) parts. Area pd24c has more and larger neurofilament-expressing neurons in layer Va and neurons in Vb form aggregates in area pv24c rather than solitary pyramids as in pd24c. Area pd24c occupies both banks of the cingulate sulcus with pv24c on the ventral bank. Layer III distinguishes these areas with pd24cd having many larger neurofilament-expressing neurons and a richer dendritic plexus in the entire layer III. Area 32 has pregenual (p32) and subgenual (s32) components. Layer II in s32 is of particular note because it has a neuron dense IIa and sparse IIb. Area 25 is comprised of anterior (25a) and posterior (25p) parts; 25p has the thinnest layer III in the cingulate gyrus and larger and more dense neurons in layer II. Area 33 continues around the genu and ventrally to encompass the full caudal extent of area 25. The multivariate, observer-interactive method accurately identified all borders except those of area 25. Finally, sACC has significantly higher GABAA, GABAB, BZ, α1, and 5-HT1A densities than pACC. The GABAB, BZ and α1 binding in the cingulate sulcus confirms the subdivision of area pd24c into ventral and dorsal components. Receptor binding also supports subdivision of area 25 with 25a containing significantly higher AMPA, kainate, NMDA, GABAA, GABAB, and α1 receptor densities than area 25p. In conclusion, ACC is comprised of two parts that are unique in terms of their cytoarchitecture and neurotransmitter receptor organization.
cytoarchitecture; neurofilament proteins; autoradiography; neurotransmitter; brain mapping; cingulate motor area; cortical layers
The frontoinsular cortex (FI) and the anterior cingulate cortex (ACC) are known to be involved in empathy for others’ pain. However, the functional roles of FI and ACC in empathetic responses have not yet been clearly dissociated in previous studies. In this study, participants viewed color photographs depicting human body parts (hands or feet) in painful or non-painful situations and performed either pain judgment (painful/non-painful) or laterality judgment (left/right) of the body parts. We found that activation of FI, rather than ACC, showed significant increase for painful compared to non-painful images, regardless of the task requirement. These findings suggest a clear functional dissociation between FI and ACC in which FI is more domain-specific than ACC in processing of empathy for pain.
empathy; fMRI; insula; anterior cingulate cortex; pain; Emotion
Emotional stimuli can be processed even when participants perceive them without conscious awareness, but the extent to which unconsciously processed emotional stimuli influence implicit memory after short and long delays is not fully understood. We addressed this issue by measuring a subliminal affective priming effect in Experiment 1 and a long-term priming effect in Experiment 2. In Experiment 1, a flashed fearful or neutral face masked by a scrambled face was presented three times, then a target face (either fearful or neutral) was presented and participants were asked to make a fearful/neutral judgment. We found that, relative to a neutral prime face (neutral–fear face), a fearful prime face speeded up participants' reaction to a fearful target (fear–fear face), when they were not aware of the masked prime face. But this response pattern did not apply to the neutral target. In Experiment 2, participants were first presented with a masked faces six times during encoding. Three minutes later, they were asked to make a fearful/neutral judgment for the same face with congruent expression, the same face with incongruent expression or a new face. Participants showed a significant priming effect for the fearful faces but not for the neutral faces, regardless of their awareness of the masked faces during encoding. These results provided evidence that unconsciously processed stimuli could enhance emotional memory after both short and long delays. It indicates that emotion can enhance memory processing whether the stimuli are encoded consciously or unconsciously.
The amygdala is known to influence processing of threat-related stimuli in distant brain regions, including visual cortex. The time-course of these distant influences is unknown, although this information is important for resolving debates over likely pathways mediating an apparent rapidity in emotional processing. To address this, we recorded event-related potentials (ERPs) to seen fearful face expressions, in preoperative patients with medial temporal lobe epilepsy who had varying degrees of amygdala pathology, plus healthy volunteers. We found that amygdala damage diminished ERPs for fearful versus neutral faces within the P1 time-range, ∼100–150 ms, and for a later component at ∼500–600 ms. Individual severity of amygdala damage determined the magnitude of both these effects, consistent with a causal amygdala role. By contrast, amygdala damage did not affect explicit perception of fearful expressions nor a distinct emotional ERP effect at 150–250 ms. These results demonstrate two distinct time-points at which the amygdala influences fear processing. The data also demonstrate that while not all aspects of expression processing are disrupted by amygdala damage, there is a crucial impact on an early P1 component. These findings are consistent with the existence of multiple processing stages or routes for fearful faces that vary in their dependence on amygdala function. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc.
ERP; medial temporal lobe epilepsy; emotion; P1; late-P3; SPM5
The dorsal anterior cingulate cortex (dACC) is commonly thought to subserve primarily cognitive functions, but has been strongly implicated in the allocation of attention to emotional information. In a previous positron emission tomography (PET) study, we observed that women with higher emotional awareness as measured by the Levels of Emotional Awareness Scale (LEAS) showed greater changes in regional cerebral blood flow (rCBF) in dACC induced by emotional films and recall. In the current study, we tested whether these effects were due to the processing of any non-neutral stimulus, or were specific to conditions of high emotional arousal. Our results extend the previous finding by demonstrating a positive correlation between emotional awareness and dACC activity only in the context of viewing highly arousing pictures. No such relationship was observed when comparing pleasant or unpleasant pictures to neutral or to each other. We also observed that the relationship between LEAS and dACC activity was present in both sexes but stronger in women than men. These results reinforce the concept that greater trait awareness of one's own emotional experiences is associated with greater engagement of the dACC during emotional arousal, which we suggest may reflect greater attentional processing of emotional information.
Most of our social interactions involve perception of emotional information from the faces of other people. Furthermore, such emotional processes are thought to be aberrant in a range of clinical disorders, including psychosis and depression. However, the exact neurofunctional maps underlying emotional facial processing are not well defined.
Two independent researchers conducted separate comprehensive PubMed (1990 to May 2008) searches to find all functional magnetic resonance imaging (fMRI) studies using a variant of the emotional faces paradigm in healthy participants. The search terms were: “fMRI AND happy faces,” “fMRI AND sad faces,” “fMRI AND fearful faces,” “fMRI AND angry faces,” “fMRI AND disgusted faces” and “fMRI AND neutral faces.” We extracted spatial coordinates and inserted them in an electronic database. We performed activation likelihood estimation analysis for voxel-based meta-analyses.
Of the originally identified studies, 105 met our inclusion criteria. The overall database consisted of 1785 brain coordinates that yielded an overall sample of 1600 healthy participants. Quantitative voxel-based meta-analysis of brain activation provided neurofunctional maps for 1) main effect of human faces; 2) main effect of emotional valence; and 3) modulatory effect of age, sex, explicit versus implicit processing and magnetic field strength. Processing of emotional faces was associated with increased activation in a number of visual, limbic, temporoparietal and prefrontal areas; the putamen; and the cerebellum. Happy, fearful and sad faces specifically activated the amygdala, whereas angry or disgusted faces had no effect on this brain region. Furthermore, amygdala sensitivity was greater for fearful than for happy or sad faces. Insular activation was selectively reported during processing of disgusted and angry faces. However, insular sensitivity was greater for disgusted than for angry faces. Conversely, neural response in the visual cortex and cerebellum was observable across all emotional conditions.
Although the activation likelihood estimation approach is currently one of the most powerful and reliable meta-analytical methods in neuroimaging research, it is insensitive to effect sizes.
Our study has detailed neurofunctional maps to use as normative references in future fMRI studies of emotional facial processing in psychiatric populations. We found selective differences between neural networks underlying the basic emotions in limbic and insular brain regions.
Individuals with schizophrenia are impaired in processing social signals such as facial expressions of emotion. Perceiving facial expressions is a complex process that depends on a distributed neural network of regions involved in affective, cognitive, and visual processing. We examined repetition priming, a non-conscious form of perceptual learning, to explore the visual-perceptual processes associated with perceiving facial expression in people with schizophrenia. Functional magnetic resonance imaging (fMRI) was also employed to probe the sensitivity of face-responsive regions in the ventral pathway to the repetition of stimuli. Subjects viewed blocks of novel and repeated faces displaying fear expressions and neutral expressions and identified each face as male or female. Gender decisions were faster for repeated encoding relative to initial encoding of faces, indicating significant priming for facial expressions. Priming was normal in schizophrenia patients, but, as expected, recognition memory for the expressions was impaired. Neuroimaging findings showed that priming-related activation for patients was reduced in the left fusiform gyrus, relative to controls, regardless of facial expression. The findings suggest that schizophrenia patients have altered neural sensitivity in regions of the ventral visual processing stream that underlie early perceptual learning of objects and faces.
Repetition priming; Face perception; Facial expression; Fusiform gyrus; Ventral visual cortex
The aim of this study was to explore social and emotional functions in patients with medial frontal damage including the anterior cingulate cortex (ACC).
Three patients with medial frontal lobe lesions primarily involving the ACC performed tasks on motivational decision making, emotional facial expression recognition, and social cognition, including theory of mind (ToM). Their performance on these tasks was compared with age and education matched healthy controls.
Patient performance on the motivational decision making and social situations tasks did not differ from controls. Selective emotional facial expression recognition impairment for fear was evident in one patient with a unilateral right ACC lesion (patient 3). ToM impairment was present in only one patient with a bilateral ACC lesion (patient 2). In contrast, the two patients with unilateral right ACC lesions had intact ToM (patients 1 and 3).
These findings suggest that medial frontal lobe lesions primarily involving the ACC do not appear to critically disrupt motivational decision making or social situation processing. The ACC plays a role in processing particular types of emotion (fear). Bilateral ACC damage impairs ToM processing, but unilateral damage to the right ACC is not sufficient to disrupt ToM.
Borderline personality disorder (BPD) is a complex psychiatric disorder that involves the core feature of affect dysregulation. Prior neuroimaging studies have indicated that BPD patients have (1) excessive amygdala activation to negative emotion and (2) diminished frontal regulation. This study examined amygdala functional connectivity in 12 women with BPD and 12 matched healthy comparison volunteers. We explored how connectivity patterns would change in the context of processing neutral, overt fear, or masked fear face expressions. Each participant underwent three 5-min fMRI scans in which they primarily viewed: (1) neutral, (2) overt fear, and (3) masked fear faces. In comparison to their healthy counterparts, young women with BPD showed (1) lower connectivity between bilateral amygdala and mid-cingulate cortex during the neutral scan; (2) higher connectivity between bilateral amygdala and rostral anterior cingulate cortex during the overt fear scan; and (3) higher right amygdala connectivity with bilateral thalamus and right caudate during the masked fear scan. Exploratory analyses revealed interesting correlations between amygdala connectivity in these conditions with multiple clinical measures. Results from the neutral scan add to the few prior connectivity studies in BPD that have been suggestive of lower fronto-limbic connectivity in BPD. However, the connectivity findings during fear processing are novel, and map onto basic research models for amygdala connectivity, that is, connections to frontal areas for overt fear processing versus connections to thalamus for automatic fear processing. Further, results suggest that BPD subjects tap into both pathways more strongly than healthy comparisons.
amygdala; borderline personality disorder; functional connectivity; functional neuroimaging; masked fear; overt fear
Effective estimation of the salience of environmental stimuli underlies adaptive behavior, while related aberrance is believed to undermine rational thought processes in schizophrenia. A network including bilateral frontoinsular cortex (FIC) and dorsal anterior cingulate cortex (dACC) has been observed to respond to salient stimuli using functional magnetic resonance imaging (fMRI). To test the hypothesis that activity in this salience network (SN) is less discriminately modulated by contextually-relevant stimuli in schizophrenia than in healthy individuals, fMRI data were collected in 20 individuals with schizophrenia and 13 matched controls during performance of a modified monetary incentive delay (MID) task. After quantitatively identifying spatial components representative of the FIC and dACC features of the SN, two principal analyses were conducted. In the first, modulation of SN activity by salience was assessed by measuring response to trial outcome. First-level general linear models were applied to individual-specific time-courses of SN activity identified using spatial independent component analysis (ICA). This analysis revealed a significant salience-by-performance-by-group interaction on the best-fit FIC component's activity at trial outcome, whereby healthy individuals but not individuals with schizophrenia exhibited greater distinction between the response to hits and misses in high salience trials than in low salience trials. The second analysis aimed to ascertain whether SN component amplitude differed between the study groups over the duration of the experiment. Independent-samples T-tests on back-projected, percent-signal-change scaled SN component images importantly showed that the groups did not differ in the overall amplitude of SN expression over the entire dataset. These findings of dysregulated but not decreased SN activity in schizophrenia provide physiological support for mechanistic conceptual frameworks of delusional thought formation.
schizophrenia; salience; cortical networks; fMRI; reward
The rostral anterior cingulated cortex (rACC) and the amygdala consistently emerge from neuroimaging studies as brain regions crucially involved in normal and abnormal fear processing. The aim of this study is to investigate a possible top-down modulation of a specific rACC sub-region on the acquisition of auditory fear conditioning.
We performed excitotoxic lesions, temporal inactivation and activation of a specific sub-region of the rACC that we identified by tracing studies as supporting most of the connectivity with the basolateral amygdala (rAmy-ACC). The effects of these manipulations over amygdala function were investigated using a classical tone-shock associative fear conditioning in the rat.
Excitotoxic lesions and transient inactivation of the rAmy-ACC pre-training selectively produced deficits in the acquisition of the tone-shock associative learning (but not context). This effect was specific for the acquisition phase and did not required protein synthesis in the rAmy-ACC. However, it could be overcome if an overtraining procedure was applied. Conversely, pre-training transient activation of the rAmy-ACC facilitated tone-shock associative learning and interfered with further extinction processes.
Our results suggest that a subregion of the rACC is key to gating the efficiency of amygdala-dependent auditory fear conditioning learning. Since rAmy-ACC inputs were confirmed to be glutamatergic, we propose that recruitment of this brain area might modulate overall BLA excitatory tone during CS-US concomitant processing. In the light of clinical research, our results provide new insight on the effect of inappropriate rACC recruitment on emotional behaviours.
anxiety; amygdala; fear acquisition; fear conditioning; anterior cingulate cortex; medial prefrontal modulation