Two electrophysiological stages of spatial orienting towards fearful faces: early temporo-parietal activation preceding gain control in extrastriate visual cortex

Visuo-spatial attention tends to be prioritized towards emotionally negative stimuli such as fearful faces, as opposed to neutral or positive stimuli. Using a covert orienting task, we previously showed that a lateral occipital P1 component, with extrastriate neural sources, was selectively enhanced to lateralized visual targets replacing a fearful face (fear-valid trial) than the same targets replacing a neutral face (fear-invalid trial), providing evidence for exogenous spatial orienting of attention towards threat cues. Here, we describe a new analysis of these data, using topographic evoked potentials mapping methods combined with a distributed source localization technique. We show that an early field topography (40-80 ms post-target onset) with a centro-parietal negativity and a left posterior parietal source distinguished fear-valid from fear-invalid trials, whereas a distinct activity with anterior cingulate sources was selectively evoked during fear-invalid trials. At the same latency, or later, no difference in field topography was found for valid compared to invalid trials with happy faces. The early parietal map preceded a modulation in amplitude of the field strength (approximately 130 ms), corresponding to the enhanced lateral occipital P1 during valid trials in the fear condition. Furthermore, this early topography at 40-80 ms was positively correlated with the subsequent amplitude modulation of P1 at 130-160 ms in the fear condition, suggesting a possible functional coupling between these two successive events. These data have important implications for models of spatial attention and interactions with emotion. They suggest two successive stages of neural activity during exogenous orienting of attention towards visual targets following fearful faces, including an early posterior parietal negativity, followed by gain control mechanisms enhancing visual responses in extrastriate occipital cortex.     

Emotion modulates the effects of endogenous attention on retinotopic visual processing

A fundamental challenge for organisms is how to focus on perceptual information relevant to current goals while remaining able to respond to goal-irrelevant stimuli that signal potential threat. Here, we studied how visual threat signals influence the effects of goal-directed spatial attention on the retinotopic distribution of processing resources in early visual cortex. We used a combined blocked and event-related functional magnetic resonance imaging paradigm with target displays comprising diagonal pairs of intact and scrambled faces presented simultaneously in the four visual field quadrants. Faces were male or female and had fearful or neutral emotional expressions. Participants attended covertly to a pair of two diagonally opposite stimuli and performed a gender-discrimination task on the attended intact face. In contrast to the fusiform face area, where attention and fearful emotional expression had additive effects, neural responses to attended and unattended fearful faces were indistinguishable in early retinotopic visual areas: When attended, fearful face expression did not further enhance responses, whereas when unattended, fearful expression increased responses to the level of attended face stimuli. Remarkably, the presence of fearful stimuli augmented the enhancing effect of attention on retinotopic responses to neutral faces in remote visual field locations. We conclude that this redistribution of neural activity in retinotopic visual cortex may serve the purpose of allocating processing resources to task-irrelevant threat-signaling stimuli while at the same time increasing resources for task-relevant stimuli as required for the maintenance of goal-directed behavior.     

Evidence for a general face salience signal in human amygdala

In the social neuroscience of face processing, multiple roles are attributed to amygdala: signalling of fear/threat-stimuli, of emotional expression, and general salience. The current study aimed at a direct comparison of amygdala activation attributable to these conditions by contrasting amygdala responses to matched emotional (threatening and non-threatening) and of non-emotional salient faces in a visual search paradigm using cartoon faces. Participants (21 healthy volunteers) had to detect a target face (angry, happy, blue, red, differing in the exact same features) in an array of closely matched non-target faces. Behavioural results revealed a pop-out effect for all targets compared to non-targets, indicating that they were all salient, independently of being emotional or non-emotional. While significant amygdala activation was obtained for all trials with salient faces (compared to those containing only non-target faces), no significant differences in activation emerged between emotional threatening, emotional non-threatening, and non-emotional targets. Moreover, right and left amygdala activation for target trials was found correlated to the behavioural measure of target detection. These findings provide evidence for a general role of the amygdala in signalling salience in a visual search independent of modality. Given the critical involvement of the amygdala in several neuropsychiatric disorders, the current findings may contribute to further our understanding on dysfunctional neural circuits in these disorders.     

fMRI of sensitization to angry faces

This study examined what is communicated by facial expressions of anger and mapped the neural substrates, evaluating the motivational salience of these stimuli. During functional magnetic resonance imaging, angry and neutral faces were presented to human subjects. Across experimental runs, signal adaptation was observed. Whereas fearful faces have reproducibly evoked response habituation in amygdala and prefrontal cortex, angry faces evoked sensitization in the insula, cingulate, thalamus, basal ganglia, and hippocampus. Complementary offline rating and keypress experiments determined an aversive rank ordering of angry, fearful, neutral, and happy faces and revealed behavioral sensitization to the angry faces. Subjects rated angry faces, in contrast to other face categories such as fear, as significantly more likely to directly inflict harm. Furthermore, they rated angry faces as significantly less likely to produce positive emotional outcomes than the other face categories. Together these data argue that angry faces, a directly aversive stimulus, produce a sensitization response.     

How efficient is the orienting of spatial attention to pain? An experimental investigation

This study investigated how efficient spatial attention was oriented to pain in 2 experiments. Participants detected whether painful (pain group) or nonpainful (control group) somatosensory stimuli were delivered to the left or right hand. Each stimulus was preceded by a visual cue presented near to the stimulated hand (valid trial), the opposite hand (invalid trial), or centrally between hands. To examine both exogenous and endogenous orienting of attention, the spatial predictability of somatosensory targets was manipulated. In the first experiment, visual cues were nonpredictive for the location of the pain stimulus, as a result of which, orienting was purely exogenous, i.e., resulting from the occurrence of the visual cue at the location of somatosensory input. In the second experiment, visual cues were spatially predictive, as a result of which, endogenous control was added, i.e., attention driven by expectations of where the somatosensory target will occur. The results showed that only in experiment 1 was spatial attention oriented more efficiently to painful compared with nonpainful somatosensory stimulation. This effect was due to faster responses on valid relative to baseline trials (engagement), rather than slower responses on invalid relative to baseline trials (disengagement), and was significantly correlated with self-reported bodily threat. In experiment 2, prioritization of the pain location was probably overridden by task strategies because it was advantageous for participants' task performance to attend to the cued location irrespective of whether stimulation was painful or not. Implications of these findings for theories of hypervigilance and attentional management of pain are discussed.     

Three stages of facial expression processing: ERP study with rapid serial visual presentation

Electrophysiological correlates of the processing facial expressions were investigated in subjects performing the rapid serial visual presentation (RSVP) task. The peak latencies of the event-related potential (ERP) components P1, vertex positive potential (VPP), and N170 were 165, 240, and 240 ms, respectively. The early anterior N100 and posterior P1 amplitudes elicited by fearful faces were larger than those elicited by happy or neutral faces, a finding which is consistent with the presence of a ‘negativity bias.’ The amplitude of the anterior VPP was larger when subjects were processing fearful and happy faces than when they were processing neutral faces; it was similar in response to fearful and happy faces. The late N300 and P300 not only distinguished emotional faces from neutral faces but also differentiated between fearful and happy expressions in lag2. The amplitudes of the N100, VPP, N170, N300, and P300 components and the latency of the P1 component were modulated by attentional resources. Deficient attentional resources resulted in decreased amplitude and increased latency of ERP components. In light of these results, we present a hypothetical model involving three stages of facial expression processing.     

Very early modulation of brain responses to neutral faces by a single prior association with an emotional context: evidence from MEG

Recent electrophysiological studies have demonstrated modulations of the very first stages of visual processing (<100 ms) due to prior experience. This indicates an influence of a memory trace on the earliest stages of stimulus processing. Here we investigated if emotional audio-verbal information associated with faces on first encounter can affect the very early responses to those faces on subsequent exposure. We recorded magneto-encephalographic (MEG) responses to neutral faces that had been previously associated with positive (happy), negative (angry) or neutral auditory verbal emotional contexts. Our results revealed a very early (30-60 ms) difference in the brain responses to the neutral faces according to the type of previously associated emotional context, with a clear dissociation between the faces previously associated to positive vs. negative or neutral contexts. Source localization showed that two main regions were involved in this very early association effect: the bilateral ventral occipito-temporal regions and the right anterior medial temporal region. These results provide evidence that the memory trace of a face integrates positive emotional cues present in the context of prior encounter and that this emotional memory can influence the very first stages of face processing. These experimental findings support the idea that face perception can be shaped by experience from its earliest stages and in particular through emotional association effects.     

Activation of the amygdala and anterior cingulate during nonconscious processing of sad versus happy faces

Previous functional neuroimaging studies have demonstrated that the amygdala activates in response to fearful faces presented below the threshold of conscious visual perception. Using a backward masking procedure similar to that of previous studies, we used functional magnetic resonance imaging (fMRI) to study the amygdala and anterior cingulate gyrus during preattentive presentations of sad and happy facial affect. Twelve healthy adult females underwent blood oxygen level dependent (BOLD) fMRI while viewing sad and happy faces, each presented for 20 ms and "masked" immediately by a neutral face for 100 ms. Masked happy faces were associated with significant bilateral activation within the anterior cingulate gyrus and amygdala, whereas masked sadness yielded only limited activation within the left anterior cingulate gyrus. In a direct comparison, masked happy faces yielded significantly greater activation in the anterior cingulate and amygdala relative to identically masked sad faces. Conjunction analysis showed that masked affect perception, regardless of emotional valence, was associated with greater activation within the left amygdala and left anterior cingulate. Findings suggest that the amygdala and anterior cingulate are important components of a network involved in detecting and discriminating affective information presented below the normal threshold of conscious visual perception.     

The neural networks underlying endogenous auditory covert orienting and reorienting

Auditory information communicated through vocalizations, music, or sounds in the environment is commonly used to orient and direct attention to different locations in extrapersonal space. The neural networks subserving attention to auditory space remain poorly understood in comparison to our knowledge about attention in the visual system. The present study investigated whether a parietal-prefrontal right-hemisphere network controls endogenous orienting and reorienting of attention to the location of sounds just as it does for visual-spatial information. Seventeen healthy adults underwent event-related functional magnetic resonance imaging (FMRI) while performing an endogenous auditory orienting task, in which peripheral cues correctly (valid) or incorrectly (invalid) specified the location of a forthcoming sound. The results showed that a right precuneus and bilateral temporal-frontal network mediated the reorienting of auditory attention at both short and long stimulus onset asynchronies (SOAs). In contrast, the more automatic stage of auditory reorienting at the shorter SOA was associated with activation in a bilateral inferior parietal-frontal oculomotor network. These findings suggest that the reorienting of auditory attention is generally supported by a similar inferior parietal-frontal network as visual attention, but in both hemispheres. However, peripheral auditory cues also appear to elicit an automatic orienting response to the spatial location of a sound followed by a period of reduced processing of information that occurs in the same location later in time.     

Neural Activation during Covert Processing of Positive Emotional Facial Expressions

Lesion studies indicate distinct neural systems for recognition of facial identity and emotion. Split-brain experiments also suggest that emotional evaluation of a stimulus can occur without conscious identification. The present study tested a hypothesis of a differential neural response, independent of explicit conscious mediation, to emotional compared to nonemotional faces. The experimental paradigm involved holding in mind an image of a face across a 45-s delay while regional cerebral blood flow was measured using positron emission tomography. Prior to the delay, a single face was presented with an explicit instruction to match it to one of two faces, photographed at different angles from the target face, presented at the end of the delay. Repeated blood flow measures were obtained while subjects held happy or neutral faces in mind or during a neutral control fixation condition without initial face presentation. The representation of emotional faces over a delay period, compared to either the nonemotional or the fixation condition, was associated with significant activation in the left ventral prefrontal cortex, the left anterior cingulate cortex, and the right fusiform gyrus. The findings support our hypothesis of a differential neural response to facial emotion, independent of conscious mediation, in regions implicated in the processing of faces and of emotions.     

Left and right occipital cortices differ in their response to spatial cueing

We investigated cue and target-related laterality effects with event-related fMRI. Both left and right occipital areas responded maximally when both cue and target were presented in the contralateral visual hemifield (VF), and minimally when cue and target were presented in the ipsilateral VF. However, whereas signal increases in right ventromedial and lateral occipital cortex were intermediate in those trials in which the cue appeared in the VF contralateral to the target (invalid cue trials), signal strength in left occipital cortex was almost identical for valid and invalid cues, i.e., high for RVF cues, and low for LVF cues, independent of the VF of the target. These data support theories which postulate a greater ability of the right hemisphere for bilateral processing. However, these laterality effects were observed earlier in the visual pathway than previously thought, leading to the question whether the hemispheric differences observed in occipital cortex are generated in the activated areas or are the effect of reentrant processes from more anterior areas, potentially in parietal cortex.     

Cerebral correlates of alerting, orienting and reorienting of visuospatial attention: an event-related fMRI study

The identification of brain systems contributing to different aspects of visuospatial attention is of both clinical and theoretical interest. Cued target detection tasks provide a simple means to dissociate attentional subcomponents, such as alerting, orienting or reorienting of attention. Event-related functional magnetic resonance imaging (fMRI) was used to study neural correlates of these distinct attentional processes. Volunteers were scanned while performing a centrally cued target detection task. Four different types of trials (no cue, neutral cue, valid cue and invalid cue trials) with targets appearing either in the right or left hemifield were randomly intermixed. Behaviourally, the data provided evidence for alerting, spatial orienting and reorienting of attention. Neurally, the alerting effect was seen in bilaterally increased extrastriatal blood oxygenation level-dependent (BOLD) activity in neutral as compared to no cue trials. Neural correlates of spatial orienting were seen in anterior cingulate cortex, which was more active during valid as compared to neutral cue trials. Neural correlates of reorienting of attention, that is, higher BOLD activity to invalid as compared to validly cued trials were evident in several brain regions including left and right intraparietal sulcus, right temporo-parietal junction and middle frontal gyrus bilaterally. The data suggest that frontal and parietal regions are specifically involved in reorienting rather than orienting attention to a spatial position. Alerting effects were seen in extrastriate regions which suggest that increased phasic alertness results in a top-down modulation of neural activity in visual processing areas.     

Getting mixed messages: The impact of conflicting social signals on the brain's target emotional response

Amidst a barrage of sensory information in the environment, the impact that individual stimuli have on our behaviour is thought to depend on the outcome of competition that occurs within and between multiple brain regions. Although biased competition models of attention have been tested in visual cortices and to a lesser extent in auditory cortex, little is known about the nature of stimulus competition outside of sensory areas. Given the hypothesized role of multiple pathways (cortical and subcortical) and specialized brain regions for processing valence information, studies involving conflicting basic emotional stimuli provide a unique opportunity to examine whether the principles of biased competition apply outside of sensory cortex. We used fMRI to examine the neural representation and resolution of emotional conflict in a sample of healthy individuals. Participants made explicit judgments about the valence of happy or fearful target facial expressions in the context of emotionally congruent, neutral, or incongruent distracters. The results suggest that emotional conflict is reflected in a dissociable manner across distinct neural regions. Posterior areas of visual cortex showed enhanced responding to congruent relative to neutral or incongruent stimuli. Orbitofrontal cortex remained sensitive to positive affect in the context of conflicting emotional stimuli. In contrast, within the amygdala, activity associated with identifying positive target expressions declined with the introduction of neutral and incongruent expressions; however, activity associated with fearful target expressions was less susceptible to the influence of emotional context. Enhanced functional connectivity was observed between medial prefrontal cortex and the amygdala during incongruent trials; the degree of connectivity was correlated with reaction time costs incurred during incongruent trials. The results are interpreted with reference to current models of emotional attention and regulation.     

Involvement of the anterior cingulate and frontoinsular cortices in rapid processing of salient facial emotional information

The anterior cingulate cortex (ACC) and frontoinsular cortex (FI) have been implicated in processing information across a variety of domains, including those related to attention and emotion. However, their role in rapid information processing, for example, as required for timely processing of salient stimuli, is not well understood. Here, we designed an emotional face priming paradigm and employed functional magnetic resonance imaging to elucidate their role in these mechanisms. Target faces with either neutral or fearful emotion were briefly primed by either neutral or fearful faces, or by blank ovals. The pregenual ACC and the FI, together with other regions, such as the amygdala, were preferentially activated in response to fearful face priming, suggesting that these regions are involved in the rapid processing of salient facial emotional information.     

Cholinergic enhancement modulates neural correlates of selective attention and emotional processing

Neocortical cholinergic afferents are proposed to influence both selective attention and emotional processing. In a study of healthy adults we used event-related fMRI while orthogonally manipulating attention and emotionality to examine regions showing effects of cholinergic modulation by the anticholinesterase physostigmine. Either face or house pictures appeared at task-relevant locations, with the alternative picture type at irrelevant locations. Faces had either neutral or fearful expressions. Physostigmine increased relative activity within the anterior fusiform gyrus for faces at attended, versus unattended, locations, but decreased relative activity within the posterolateral occipital cortex for houses in attended, versus unattended, locations. A similar pattern of regional differences in the effect of physostigmine on cue-evoked responses was also present in the absence of stimuli. Cholinergic enhancement augmented the relative neuronal response within the middle fusiform gyrus to fearful faces, whether at attended or unattended locations. By contrast, physostigmine influenced responses in the orbitofrontal, intraparietal and cingulate cortices to fearful faces when faces occupied task-irrelevant locations. These findings suggest that acetylcholine may modulate both selective attention and emotional processes through independent, region-specific effects within the extrastriate cortex. Furthermore, cholinergic inputs to the frontoparietal cortex may influence the allocation of attention to emotional information.     

The adaptive threat bias in anxiety: amygdala-dorsomedial prefrontal cortex coupling and aversive amplification

Functionally, anxiety serves to increase vigilance towards aversive stimuli and improve the ability to detect and avoid danger. We have recently shown, for instance, that anxiety increases the ability to a) detect and b) instigate defensive responses towards aversive and not appetitive face stimuli in healthy individuals. This is arguably the key adaptive function of anxiety, yet the neural circuitry underlying this valence-specific effect is unknown. In the present translational study, we sought evidence for the proposition that dorsomedial regions of the prefrontal (DMPFC) and cingulate cortex constitute the human homologue of the rodent prelimbic and are thus associated with increased amygdala responding during this adaptive threat bias in anxiety. To this end, we applied a novel functional connectivity analysis to healthy subjects (N=20) identifying the emotion of fearful and happy faces in an fMRI scanner under anxious (threat of unpredictable foot shock) and non-anxious (safe) conditions. We showed that anxiety significantly increased positive DMPFC-amygdala connectivity during the processing of fearful faces. This effect was a) valence-specific (it was not seen for happy faces), b) paralleled by faster behavioral response to fearful faces, and c) correlated positively with trait anxiety. As such we provide the first experimental support for an anxiety-mediated, valence-specific, DMPFC-amygdala aversive amplification mechanism in healthy humans. This may be homologous to the rodent prelimbic-amygdala circuit and may, given the relationship with trait anxiety, underlie vulnerability to anxiety disorders. This study thus pinpoints a key neural mechanism in adaptive anxiety and highlights its potential link to maladaptive anxiety.     

Parallel amygdala and inferotemporal activation reflect emotional intensity and fear relevance

Much research demonstrates that emotional stimuli prompt increased amygdala and visual cortical activation. Here we measure functional activity in the visual cortex and amygdala with fMRI while selected fearful and control participants view a range of neutral, emotionally arousing, and fear-relevant pictures. BOLD signal in the amygdala and inferotemporal visual cortex closely covaried during emotional picture viewing, increasing systematically with rated picture arousal. Furthermore, fearful individuals reacting to specific fear cues show parallel, heightened activation in these two structures compared with non-fearful controls. The findings suggest an individually-sensitive, positive linear relationship between the arousing quality of visual stimuli and activation in amygdala and ventral visual cortex, supporting the hypothesized functional connectivity described in the animal model.     

Neuroanatomical dissociation between bottom-up and top-down processes of visuospatial selective attention

Allocation of attentional resources to portions of the available sensory input can be regulated by bottom-up processes, i.e., spontaneous orientation towards an oncoming stimulus (stimulus-driven attention), and by top-down processes, i.e., intentionally and driven by knowledge, expectation and goals. The present study aimed at advancing the understanding of brain networks mediating bottom-up and top-down control of visuospatial attention by employing a paradigm that parametrically varied demands on these two processes. Spatial predictability of peripheral targets was parametrically varied by centrally cueing one, two, three or four of four possible locations. Reaction time decreased linearly with more precise valid cueing of the target location and increased with more precise invalid cueing. Event-related functional magnetic resonance imaging (fMRI) enabled measurement of blood oxygenation level-dependent (BOLD) responses to cues and to targets. A mostly left-hemispheric network consisting of left intraparietal sulcus, inferior and superior parietal lobule, bilateral precuneus, middle frontal gyri including superior frontal sulci, and middle occipital gyri displayed BOLD responses to cues that increased linearly with more precise spatial cueing, indicating engagement by top-down spatial selective attention. In contrast, bilateral temporoparietal junction, cingulate gyrus, right precentral gyrus and anterior and posterior insula, bilateral fusiform gyri, lingual gyri and cuneus displayed BOLD responses to targets that increased with their spatial unpredictability, indicating engagement by stimulus-driven orienting. The results suggest two largely dissociated neural networks mediating top-down and bottom-up control of visuospatial selective attention.     

Processing of unattended facial emotions: a visual mismatch negativity study

Facial emotions express our internal states and are fundamental in social interactions. Here we explore whether the repetition of unattended facial emotions builds up a predictive representation of frequently encountered emotions in the visual system. Participants (n=24) were presented peripherally with facial stimuli expressing emotions while they performed a visual detection task presented in the center of the visual field. Facial stimuli consisted of four faces of different identity, but expressed the same emotion (happy or fearful). Facial stimuli were presented in blocks of oddball sequence (standard emotion: p=0.9, deviant emotion: p=0.1). Event-related potentials (ERPs) to the same emotions were compared when the emotions were deviant and standard, respectively. We found visual mismatch negativity (vMMN) responses to unattended deviant emotions in the 170-360 ms post-stimulus range over bilateral occipito-temporal sites. Our results demonstrate that information about the emotional content of unattended faces presented at the periphery of the visual field is rapidly processed and stored in a predictive memory representation by the visual system. We also found evidence that differential processing of deviant fearful faces starts already at 70-120 ms after stimulus onset. This finding shows a 'negativity bias' under unattended conditions. Differential processing of fearful deviants were more pronounced in the right hemisphere in the 195-275 ms and 360-390 ms intervals, whereas processing of happy deviants evoked larger differential response in the left hemisphere in the 360-390 ms range, indicating differential hemispheric specialization for automatic processing of positive and negative affect.     

Adolescent immaturity in attention-related brain engagement to emotional facial expressions

Selective attention, particularly during the processing of emotionally evocative events, is a crucial component of adolescent development. We used functional magnetic resonance imagining (fMRI) with adolescents and adults to examine developmental differences in activation in a paradigm that involved selective attention during the viewing of emotionally engaging face stimuli. We evaluated developmental differences in neural activation for three comparisons: (1) directing attention to subjective responses to fearful facial expressions relative to directing attention to a nonemotional aspect (nose width) of fearful faces, (2) viewing fearful relative to neutral faces while attending to a nonemotional aspect of the face, and (3) viewing fearful relative to neutral faces while attention was unconstrained (passive viewing). The comparison of activation across attention tasks revealed greater activation in the orbital frontal cortex in adults than in adolescents. Conversely, when subjects attended to a nonemotional feature, fearful relative to neutral faces influenced activation in the anterior cingulate more in adolescents than in adults. When attention was unconstrained, adolescents relative to adults showed greater activation in the anterior cingulate, bilateral orbitofrontal cortex, and right amygdala in response to the fearful relative to neutral faces. These findings suggest that adults show greater modulation of activity in relevant brain structures based on attentional demands, whereas adolescents exhibit greater modulation based on emotional content.